cas 5351-23-5, 4-Hydroxybenzhydrazide | Articles data

Articles about 5351-23-5Total 124 be found

Article title
Article abstract
Author
Journal number and time
Download

Synthesis, characterization and antioxidant activity of new dibasic tridentate ligands: X-ray crystal structures of DMSO adducts of 1,3-dimethyl-5-acetyl-barbituric acid o-hydroxybenzoyl hydrazone copper(II) complex
o-Hydroxybenzoyl hydrazine and p-hydroxybenzoyl hydrazine react with 1,3-dimethyl-5-acetyl-barbituric acid in ethanol to give H2L 1 (85% yield) and H2L2 (91% yield) respectively. The copper(II) complexes with DMSO adducts, [Cu(L 1)(DMSO)] and [Cu(L2)(DMSO)], were prepared by the stoichiometric reaction of the CuCl2·5H2O with the H2L1 and H2L2 in a molar ratio (M:L) of 1:1 in DMSO/water mixture. All compounds have been fully characterized using conventional spectroscopic techniques. X-ray structure analysis was carried out on the [Cu(L1)(DMSO)] which crystallizes in the triclinic P-1 space group. In addition, both ligands were applied several antioxidant assays including total antioxidant activity by phosphomolybdate, ferric reducing antioxidant power (FRAP) and scavenging activity on 1,1-diphenyl-2- picrylhydrazyl (DPPH). The results from antioxidant assays have shown that both ligands have excellent activities.
Giziroglu, Emrah,Aygün, Muhittin,Sarikurkcu, Cengiz,Kazar, Didem,Orhan, Nil,Firinci, Erkan,Soyleyici, H. Can,Gokcen, Ceren
p. 199 - 205
(2013)
Read Online

Synthesis of 1,2,4-triazole-functionalized solid support and its use in the solid-phase synthesis of trisubstituted 1,2,4-triazoles
(Matrix Presented) 1,2,4-Triazoles were synthesized on a solid support in three steps, with excellent yields and purities. The utility of this triazole-functionalized solid support was demonstrated by the solid-phase synthesis of various trisubstituted 1,2,4-triazoles.
Katritzky, Alan R.,Qi, Ming,Feng, Darning,Zhang, Guifeng,Griffith, Michael C.,Watson, Karen
p. 1189 - 1191
(1999)
Read Online

Seven coordinated cobalt(II) complexes with 2,6-diacetylpyridine bis(4-acylhydrazone) ligands: Synthesis, characterization, DNA-binding and nuclease activity
A new series of pentadentate 2,6-diacetylpyridine bis(4-acylhydrazone)s (H2L1 and H2L2) based seven-coordinated cobalt(II) complexes, [Co(Ln)X2] (n = 1 and X = DMF for (1); n = 2 and X = H2O for (2)); [Co(H2Ln)Y2] (n = 1 or 2; Y = N3- or NCS-), has been synthesized and characterized by using spectroscopic techniques. Single crystal X-ray study of [Co(L1)(DMF)2] (1) complex exhibits pentagonal-bipyramidal coordination geometry where the pentadentate N3O2 ligand in the equatorial plane of the bipyramid and two dimethylformamide molecules in the axial area. Interaction of the cobalt(II) complexes with CT DNA has been investigated by absorption titration method and viscosity measurements which reveal that the cobalt(II) complexes could bind with CT DNA through intercalation. Cleavage activity of the complexes (1) and (2) with pBR 322 plasmid DNA was evaluated by agarose gel electrophoresis demonstrating that the ability of the complexes to cleave the pBR 322 plasmid DNA via oxidative pathway, possibly due to the involvement of a diffusible hydroxyl radical mechanism in presence and absence of an oxidative agent. The nuclease activity of the Co(II) complexes has strong dependence on the concentration of complex and reaction time, both in presence and absence of hydrogen peroxide.
G?k?e, Cansu,Dilek, Nefise,Gup, Ramazan
p. 213 - 220
(2015)
Read Online

Copper(II) complexes with 4-hydroxyacetophenone-derived acylhydrazones: Synthesis, characterization, DNA binding and cleavage properties
Two new Cu(II) complexes of Schiff base-hydrazone ligands, hydroxy-N′-[(1Z)-1-(4-hydroxyphenyl)ethylidene]benzohydrazide [H 3L1] and ethyl 2-(4-(1-(2-(4-(2-ethoxy-2-oxoethoxy) benzoyl)hydrazono)ethyl)phenoxy)acetate (HL2) have been synthesized and then characterized by microcopy and spectral studies. X-ray powder diffraction illustrates that [Cu(L2)2] complex is crystalline in nature whereas [Cu(H2L1) 2]·2H2O has an amorphous structure. Binding of the copper complexes with Calf thymus DNA (CT-DNA) has been investigated by UV-visible spectra, exhibiting non-covalent binding to CT-DNA. DNA cleavage experiments have been also investigated by agarose gel electrophoresis in the presence and absence of an oxidative agent (H2O2). The effect of complex concentration on the DNA cleavage reaction has been also studied. Both copper complexes show nuclease activity, which significantly depends on concentrations of the complexes, in the presence of H 2O2 through oxidative mechanism whereas they slightly cleavage DNA in the absence an oxidative agent.
Gup, Ramazan,G?k?e, Cansu,Aktürk, Sel?uk
p. 484 - 492
(2015)
Read Online

Seven-coordinated cobalt(II) complexes with 2,6-diacetylpyridine bis(4-hydroxybenzoylhydrazone): Synthesis, characterisation, DNA binding and cleavage properties
Synthesis and characterisation of three seven-coordinated cobalt(II) complexes of 2,6-diacetylpyridine bis(4-hydroxybenzoylhydrazone) (H4L) ligand, [Co(H2L)(H2O)2] (1), [Co(H4L)(N3)2] (2) and [Co(H4L)(NCS)2] (3) are described. The structures of the complexes were characterised by elemental analysis, IR, UV-vis and magnetic susceptibility measurement. The molecular structure of the [Co(H4L)(NCS)2] (3) was also determined by X-ray crystallography. Single crystal X-ray revealed that the Co(II) complex (3) has a pentagonal-bipyramidal coordination geometry, with pentadentate N3O2 ligand in the equatorial plane of the bipyramid and two isothiocyanato groups in the axial area. Interaction of the cobalt(II) complexes with CT-DNA was investigated by absorption titration method and viscosity measurements. Cleavage activity of the complexes with pBR 322 plasmid DNA was evaluated by agarose gel electrophoresis in presence and absence of an oxidative agent, and the mechanism of DNA cleavage was investigated. The results suggest that the cobalt(II) complexes bind effectively and they exhibit nuclease activity, which has strong dependence on the concentration of complex and reaction time, both in presence and absence of hydrogen peroxide.
Gup, Ramazan,G?k?e, Cansu,Dilek, Nefise
p. 629 - 641
(2015)
Read Online

Mn(II) catalyzed synthesis of 5(4-hydroxyphenyl)-2-(N-phenylamino)-1,3,4-oxadiazole: Crystal structure, DFT, molecular docking, Hirshfeld surface analysis, and in vitro anticancer activity on DL cells
The syntheses and screening of novel synthetic molecules have gained attention as a potential therapeutic agent in the treatment of cancer. In the present study, a new compound 5(4-hydroxyphenyl)-2-(N-phenylamino)-1,3,4-oxadiazole (Hppo) has been synthesized and its anticancer activity is investigated against Dalton's lymphoma (DL) tumor cells derived from murine T-cell lymphoma. The Hppo has been characterized through IR, NMR, and single-crystal X-ray data. The structure of Hppo is stabilized via hydrogen bonding interactions and crystallizes in an orthorhombic system with space group P b c n. The fingerprint plots associated with Hirshfeld surface analysis indicate that there are different types of weak interactions viz. C-H···N, O-H···N and C-H···O. The DFT calculations are also performed to verify physiochemical properties of Hppo and the results obtained are in good agreement with the experimental results. The HOMO and LUMO energy gap of 7.344 eV for Hppo indicates good NLO properties. The cytotoxicity activity of Hppo is tested against Dalton's lymphoma cells using MTT assay which reveals that the compound showed admirable anticancer activity (IC50= 50 μg/mL), which is better than many previously reported compounds. The mechanism of action of Hppo is investigated by performing different biological studies and the results obtained reveal that Hppo acts through down-regulating mitochondrial membrane potential and up-regulating reactive oxygen species production. Molecular docking studies are also performed to obtain more insights on biological activities of Hppo and its mode of action against CYP-19 (PDB: 3EQM), JAK2 (PDB: 5AEP), BCL-2 (PDB: 2O2F), and caspase3 (PDB: 1RE1), and result displayed favorable binding interactions with binding energy -7.43, -7.96, -6.61, and -6.88 Kcal/mol.
Acharya, A.,Bharty, M. K.,Butcher, R. J.,Gond, M. K.,Katiyar, D.,Maiti, B.,Pandey, Shivendra Kumar,Shukla, Alok,Tiwari, N.
(2021/10/04)

Pleuromutilin derivative with 1, 3, 4-oxadiazole side chain and preparation and application thereof
The invention belongs to the field of medicinal chemistry, and particularly relates to a pleuromutilin derivative with a 1, 3, 4-oxadiazole side chain and preparation and application thereof The pleuromutilin derivative with the 1, 3, 4-oxadiazole side chain is a compound shown in a formula 2 or a pharmaceutically acceptable salt thereof, and a solvent compound, an enantiomer, a diastereoisomer and a tautomer of the compound shown in the formula 2 or the pharmaceutically acceptable salt thereof or a mixture of the solvent compound, the enantiomer, the diastereoisomer and the tautomer in any proportion, including a racemic mixture. The pleuromutilin derivative has good antibacterial activity, is especially suitable for being used as a novel antibacterial agent for systemic system infection of animals or human beings, and has good water solubility.
-
Paragraph 0055-0056; 0070; 0090; 0093; 0095; 0103

(2021/07/24)

Novel arylcarbamate-N-acylhydrazones derivatives as promising BuChE inhibitors: Design, synthesis, molecular modeling and biological evaluation
A novel series of arylcarbamate-N-acylhydrazones derivatives have been designed and synthesized as potential anti-cholinesterase agents. In vitro studies revealed that these compounds demonstrated selective for butyrylcholinesterase (BuChE) with potent inhibitory activity. The compounds 10a-d, 12b and 12d were the most potent BuChE inhibitors with IC50 values of 0.07–2.07 μM, highlighting the compound 10c (IC50 = 0.07 μM) which showed inhibitory activity 50 times greater than the reference drug donepezil (IC50 = 3.54 μM). The activity data indicates that the position of the carbamate group in the aromatic ring has a greater influence on the inhibitory activity of the derivatives. The enzyme kinetics studies indicate that the compound 10c has a non-competitive inhibition against BuChE with Ki value of 0.097 mM. Molecular modeling studies corroborated the in vitro inhibitory mode of interaction and show that compound 10c is stabilized into hBuChE by strong hydrogen bond interaction with Tyr128, π-π stacking interaction with Trp82 and CH?O interactions with His438, Gly121 and Glu197. Based on these data, compound 10c was identified as low-cost promising candidate for a drug prototype for AD treatment.
Yamazaki, Diego A.S.,Rozada, Andrew M.F.,Baréa, Paula,Reis, Elaine C.,Basso, Ernani A.,Sarragiotto, Maria Helena,Seixas, Flávio A.V.,Gauze, Gisele F.
(2021/01/18)

Design, synthesis, in vitro and in vivo evaluation against MRSA and molecular docking studies of novel pleuromutilin derivatives bearing 1, 3, 4-oxadiazole linker
A class of pleuromutilin derivatives containing 1, 3, 4-oxadiazole were designed and synthesized as potential antibacterial agents against Methicillin-resistant staphylococcus aureus (MRSA). The ultrasound-assisted reaction was proposed as a green chemistry method to synthesize 1, 3, 4-oxadiazole derivatives (intermediates 85–110). Among these pleuromutilin derivatives, compound 133 was found to be the strongest antibacterial derivative against MRSA (MIC = 0.125 μg/mL). Furthermore, the result of the time-kill curves displayed that compound 133 could inhibit the growth of MRSA in vitro quickly (- 4.36 log10 CFU/mL reduction). Then, compound 133 (- 1.82 log10 CFU/mL) displayed superior in vivo antibacterial efficacy than tiamulin (- 0.82 log10 CFU/mL) in reducing MRSA load in mice thigh model. Besides, compound 133 exhibited low cytotoxicity to RAW 264.7 cells. Molecular docking studies revealed that compound 133 was successfully localized in the binding pocket of 50S ribosomal subunit (ΔGb = -10.50 kcal/mol). The results indicated that these pleuromutilin derivatives containing 1, 3, 4-oxadiazole might be further developed into novel antibiotics against MRSA.
Liu, Jie,Zhang, Guang-Yu,Zhang, Zhe,Li, Bo,Chai, Fei,Wang, Qi,Zhou, Zi-Dan,Xu, Ling-Ling,Wang, Shou-Kai,Jin, Zhen,Tang, You-Zhi
(2021/05/17)

Novel phenolic Mannich base derivatives: synthesis, bioactivity, molecular docking, and ADME-Tox Studies
In this study, it was aimed to synthesize novel molecules containing potential biological active phenolic Mannich base moiety and evaluate the inhibition properties against α-glycosidase (α-Gly) and acetylcholinesterase (AChE). For this purpose, phenolic aldehydes (1–3) were synthesized from 4-hydroxy-3-methoxy benzaldehyde (vanillin) according to the Mannich Reaction. Five different carboxylic acid hydrazides (4a-e) were synthesized from esters obtained from carboxylic acids. Fifteen Schiff base derivatives (5a-e, 6a-e, and 7a-e) were synthesized from the condensation reaction of compounds 1–3 with 4a-e. In this work, a series of novel Schiff bases from Phenolic Mannich bases (5a-e, 6a-e, and 7a-e) were tested toward α-Gly and AChE enzymes. Compounds 5a-e, 6a-e, and 7a-e showed Kis in ranging of 341.36 ± 31.84–904.76 ± 93.56?nM on AChE and 176.27 ± 22.87—621.77 ± 69.98?nM on α-glycosidase. Finally, novel compounds were found using molecular docking method to calculate the biological activity of these bases against many enzymes. The enzymes used in these calculations are acetylcholinesterase and α-glycosidase, respectively. Molecule 6b is more effective and active than other molecules with a docking score parameter value of ? 8.77 against AChE enzyme and 6d is more effective and active than other molecules with a docking score parameter value of ? 4.94 against α-Gly enzyme. After calculating the biological activities of novel compounds, ADME/T analysis parameters were examined to calculate the future drug use properties.
?endil, K?v?lc?m,Demircio?lu, ?brahim Hakk?,Gül?in, ?lhami,Taslimi, Parham,Tokal?, Feyzi Sinan,Tuzun, Burak
(2021/07/12)

Synthesis, characterization and computational study of N-acylhydrazone derivatives
The N-Acylhydrazone of benzoic acid and their derivatives are important intermediates in organic synthesis and have widespread applications in the medicinal industry. The N-Acylhydrazone was prepared through the condensing the phenyl hydrazide derivatives which prepared from phenylmethyl ester, with benzaldehyde and then identified by physicochemical properties and spectral analysis; FT-IR and 1HNMR. Computation calculations studies by using Semi-empirical-PM3 method through a molecular structure with optimized geometry showed that there is a high correlation between dipole moment, Electron affinity (EA), ionization potential (IP), electronegativity, ClogP and hardness. To Proof, the stability of N-Acylhydrazone derivatives by using Molecular orbital calculations supported a full description of the orbitals and the contributions of individual atoms. Highest occupied molecular orbital/lowest unoccupied molecular orbital energies and structures are demonstrated, calculation atomic charge and molecular electrostatic potential. Through the data obtained from the computational chemistry program, Hyper Chem 8, we were able to demonstrate that the N-acylhydrazone derivatives have a close values and within the limits of stability.
Alrubaie, Leaqaa A. Raheem
p. 5067 - 5075
(2021/08/31)

Using m icrowave and ultrasound to synthesis of substituted bis-acyl hydrazone derivatives
In this paper, some new bis-acyl hydrazone derivatives (4a-f) were prepared through the reaction of carboxylic acid hydrazides with 1,4-diacetylbenzene using classical methods, microwave and ultrasound irradiation methods. These compounds are obtained through a series of reactions where some carboxylic acids react with ethanol first in the presence of concentrated sulfuric acid to give the corresponding esters (2a-f), which when treatment with aqueous hydrazine give carboxylic acid hydrazides (3a-f).thus, The results proved that the use of microwave and ultrasound techniques is much better than the classical methods, as it gave a higher yield, shorter reaction time, and the absence of the use of solvents. All newly synthesized compounds were confirmed by IR, (1H & 13C) NMR spectral analysis and the corresponding reactions were monitored by TLC using the reported eluent.
Mohammed, Salim J.,Sheat, Attallah M.,A.abood, Salih,Yahya, Omar M.
p. 6423 - 6427
(2021/11/01)

Synthesis, in silico, in vitro and in vivo evaluations of isatin aroylhydrazones as highly potent anticonvulsant agents
In this study, a series of new isatin aroylhydrazones (5a-e and 6a-e) was synthesized and evaluated for their anticonvulsant activities. The (Z)-configuration of compounds was confirmed by 1H NMR. In vivo studies using maximal electroshock (MES) and pentylenetetrazole (PTZ) models of epilepsy in mice revealed that while most of compounds had no effect on chemically-induced seizures at the higher dose of 100 mg/kg but showed significant protection against electrically-induced seizures at the lower dose of 5 mg/kg. Certainly, N-methyl analogs 6a and 6e were found to be the most effective compounds, displaying 100% protection at the dose of 5 mg/kg. Protein binding and lipophilicity (logP) of the selected compounds (6a and 6e) were also determined experimentally. In silico evaluations of title compounds showed acceptable ADME parameters, and drug-likeness properties. Distance mapping and docking of the selected compounds with different targets proposed the possible action of them on VGSCs and GABAA receptors. The cytotoxicity evaluation of 6a and 6e against SH-SY5Y and Hep-G2 cell lines indicated safety profile of compounds on the neuronal and hepatic cells.
Emami, Saeed,Valipour, Mehdi,Kazemi Komishani, Fatemeh,Sadati-Ashrafi, Fatemehsadat,Rasoulian, Maria,Ghasemian, Majid,Tajbakhsh, Mahmood,Honarchian Masihi, Patrick,Shakiba, Aidin,Irannejad, Hamid,Ahangar, Nematollah
(2021/05/10)

Manganese(II) catalyzed synthesis of bis(N-cyclohexylthiourea) derived from thiosemicarbazide: Structural characterization, fluorescence, cyclic voltammetry, Hirshfeld surface analysis and DFT calculation
A new compound bis(N-cyclohexylthiourea) (H2chth) has been synthesized and characterized with the aid of elemental analyses, IR, NMR and single crystal X-ray diffraction data. Compound H2chth crystallizes in triclinic system with space group P-1. During the course of reaction, the cyclohexyl isothiocynate moiety of the substituted thiosemicarbazide undergoes tautomerization and rearrangement into the corresponding carbothioamide moiety in the presence of manganese(II) acetate. The interaction of H2chth with different metal ions in methanol solution is studied and it shows interesting red shifts with Mn2+, Co2+, Ni2+, Cu2+, Zn2+ and Cd2+ ions which suggests that compound H2chth may be a useful probe for sensing of these metal ions. Cyclic voltammetric studies of H2chth and its interaction with different metal ions exhibit complete irreversible redox behavior. Compound H2chth exhibits emission at 27322 cm?1 upon excitation at 37037 cm?1. The emission spectra of different metal ions with H2chth exhibit less intense emissions as compared to the free H2chth. The structure of compound H2chth is stabilized via intermolecular N-H···S and C-H···S hydrogen bonding. The geometry of the compound H2chth has been optimized using the B3LYP density functional theory method and the results are compared with the X-ray diffraction data. The calculated geometrical parameters corroborate with the experimental data. Frontier molecular orbital analysis suggests that compound H2chth is soft and highly reactive. Hirshfeld surface map and 2D finger print plot were used to explore the intermolecular interactions of H2chth.
Bharty, M. K.,Butcher, R. J.,Gond, M. K.,Jaiswal, S.,Krishnamoorthi, S.,Maiti, B.
(2021/07/31)

Pyrazole derivatives of medically relevant phenolic acids: Insight into antioxidative and anti-lox activity
Background: From the point of view of medicinal chemistry, compounds containing phenolic and pyrazolic moiety are significant since they are often constituents of bioactive compounds. Objective: The aims of this study were to synthesize pyrazole derivatives of medically relevant phenolic acids, confirm their structure, and evaluate their antioxidative and anti-LOX activities. Methods: Phenolic pyrazole derivatives were obtained, starting from esters of medically relevant phenolic acids. The structures of all obtained compounds were determined by NMR and IR spectroscopy, and UV-Vis spectrophotometry. In addition, the single-crystal X-ray diffraction was used. Pyrazole derivatives were tested for their in vitro antioxidative (DPPH assay), and lipoxygenase (LOX) inhibitory ac-tivities. Radical quenching mechanism was estimated using DFT and thermodynamic approach, while molecular docking was used to estimate the binding mode within the enzyme. Results: Pyrazole derivatives were obtained in high yields. The crystal structure of a new compound 3e was determined. Pyrazole derivative with catechol moiety 3d exhibited excellent radical scavenging ac-tivity, while compound 3b exhibited the best anti-LOX activity. Molecular docking study revealed that there is no direct interaction of any ligand with the active site of LOX-Ib, but pyrazoles 3a-e behave as inhibitors blocking the approach of linoleic acid to the active site. Conclusion: In this research, protocatechuic and vanillic acid pyrazole derivatives have been obtained for the first time. In vitro antioxidative assay suggests that pyrazole derivate of protocatechuic acid is a powerful radical scavenger, while anti-LOX assay indicates a pyrazole derivative with 4-hydroxyphenyl moiety.
Bogdanovi?, Goran A.,Brankovi?, Jovica,Milovanovi?, Vesna,Mladenovi?, Milan,Novakovi?, Sla?ana,Petrovi?, Vladimir P.,Petrovi?, Zorica D.,Simijonovi?, Du?ica
p. 807 - 819
(2021/10/21)

Molecular docking studies, biological evaluation and synthesis of novel 3-mercapto-1,2,4-triazole derivatives
Abstract: Synthesis of bioactive heterocyclic compounds having effective biological activity is an essential research area for wide-ranging applications. In this study, a conventional methodology has been developed for the synthesis of a series of new 3-mercapto-1,2,4-triazole derivatives 4a–f. The purity and structure of the synthesized molecules were confirmed by 1H NMR, 13C NMR and elemental analysis. In addition, the prepared compounds were screened for their anti-proliferative activity against three human cancer cell lines including A549 (lung cancer), MCF7 (breast cancer) and SKOV3 (ovarian cancer) using MTT reduction assay. All the tested compounds demonstrated remarkable cytotoxic activity with IC50 values ranging from 3.02 to 15.37?μM. The heterocyclic compound bearing 3,4,5-trimethoxy moiety was found to be the most effective among the series displaying an IC50 of 3.02?μM specifically against the ovarian carcinoma cancer cell line (SKOV3). Moreover, Annexin V-FITC/propidium iodide staining assay indicated that this compound can induce apoptosis in SKOV3 cells. Furthermore, cell cycle assay showed a significant cell cycle arrest at the G2/M phase in a dose-dependent manner for this compound. The molecular docking results was showed binding modes of potent compound 4d perfectly corroborated the suggestion of binding to the colchicine site. The entire results conclude that 3-mercapto-1,2,4-triazole derivatives can be synthesized by a green method for biological and pharmacological applications. Graphic abstract: New analogs of 3-mercapto-1,2,4-triazole potential derivatives for anti-proliferative activity were synthesized. Cytotoxic activity of all synthesized compounds was evaluated against tree human cancer cell lines: lung (A549), breast (MCF7) and ovarian (SKOV3).[Figure not available: see fulltext.].
Ghanaat, Javad,Khalilzadeh, Mohammad A.,Zareyee, Daryoush
p. 223 - 232
(2020/02/25)

Synthesis, crystallographic, computational and molecular docking studies of new acetophenone-benzoylhydrazones
Three aroylhydrazones, acetophenone-Benzoylhydrazone (I), p-hydroxy-acetophenone-benzoylhydrazone (II) and p-nitro- acetophenone-benzoylhydrazone (III) have been synthesized and further analyzed with the aid of IR, UV-Vis, and NMR spectroscopic and X-ray Crystallographic techniques. The optimized molecular structures were determined by Density Functional Theory (DFT) using the B3LYP function comprising the 6-311++G (2d, 2p) basis set. The calculated and experimental results for the NMR spectroscopic technique were observed to be consistent. The two reported crystals are monoclinic in the same space group of P21/c. Hirshfeld surface analyses revealed H···H as the most important intermolecular interactions in compounds II and III. The molecular docking of the compounds against three enzymes - aldose reductase, aldehyde reductase, and β-glucosidase were also carried out where compound III displayed the best inhibition of the enzymes with a binding energy of -11.30, -9.58 and -11.10 Kcal mol?1 against aldose reductase, aldehyde reductase, and β- glucosidase respectively.
Ajayeoba, Temitope A.,Woods, Joseph O.,Ayeni, Ayowole O.,Ajayi, Tomilola J.,Akeem, Raji A.,Hosten, Eric C.,Akinyele, Olawale F.
(2021/04/15)

Synthesis, Antiproliferative and Antioxidant Activity of 3-Mercapto-1,2,4-Triazole Derivatives as Combretastatin A-4 Analogues
Two series of 3-mercapto-1,2,4-triazole derivatives containing alkoxy substituents different in size and position were synthesized and their structures were characterized by FT-IR, 1H NMR, 13C NMR spectroscopy and elemental analysis. The synthesized compounds were assessed for their antiproliferative activity against colon cancer cell line (SW480). The results indicated that the size and position of the alkoxy group significantly influenced the antiproliferative activity. The highest cancer cell growth inhibition values were observed for the compounds containing 3,4,5-trimethoxyphenyl groups in their structures (57.74, 54.14 and 60.70% at 50 μM for compounds 5a, 12b and 14, respectively). The synthesized compounds were also subjected to DPPH protocol for evaluating the antioxidant activity. The results showed that all compounds had moderate to high levels of antioxidant capacity as compared to ascorbic acid as standard, the highest free radical scavenging capacity of 75% was observed for compound 4a at 50 μM.
Al-Mansury, Sadiq,Balakit, Asim A.,Alkazazz, Fatin Fadhel,Ghaleb, Rana A.
p. 556 - 565
(2021/09/28)

Aromatic acyl hydrazone derivative and application thereof as NA inhibitor
The invention relates to an aromatic acyl hydrazone derivative as shown in a structural formula I, pharmaceutically acceptable salt and a pharmaceutical composition thereof, and application of the aromatic acyl hydrazone derivative and the pharmaceutically acceptable salt and the pharmaceutical composition in preparation of an influenza virus neuraminidase inhibitor, wherein R is one of trifluoromethyl, nitryl, 3-methyl-4-nitryl, 3-hydroxyl-4-nitryl, 3-nitryl-4-hydroxyl, hydroxyl, dihydroxyl, dinitryl, 3-methoxy-4-hydroxyl or trihydroxyl; Y is selected from hydroxyl, dihydroxyl, 2-hydroxyl-3-methoxy, 2-hydroxyl-4-methoxy,2-hydroxyl-5-methoxy,2-hydroxyl-6-methoxy,3-hydroxyl-2-methoxy,3-hydroxyl-4-methoxy,3-hydroxyl-5-methoxy,3-hydroxyl-6-methoxy,4-hydroxyl-2-methoxy,4-hydroxyl-3-methoxy,4-hydroxyl-3,5-dimethoxy, trihydroxyl, 4-hydroxyl-3-ethoxy, or 4-hydroxyl-3,5-dimethoxy; w is selected from CH or N; and z is selected from CH or N.
-
Paragraph 0039; 0044-0046; 0181-0185

(2020/12/30)

Design, synthesis, and antimicrobial evaluation of some nifuroxazide analogs against nosocomial infection
A series of 10 p-substitutedbenzoylmethylene hydrazide derivatives 4a-j were synthesized by protecting carboxylic group of 4-hydroxybenzoic acid using methanol and sulfuric acid than reacting it with hydrazide to form 4-hydroxybenzohydrazide followed by reacting with a variety of aldehydes and evaluated for their activity against nosocomial infection. All the synthesized compounds were characterized by Fourier-transform infrared (FT-IR), 1H nuclear magnetic resonance (NMR), and mass spectral data. The in vitro antimicrobial potential of synthesized compounds was estimated against prominent strains of nosocomial pathogens (Staphylococcus aureus, Escherichia coli, and Aspergillus niger). The antimicrobial evaluation revealed compounds 4b, 4c, 4d, 4e, 4f, and 4j to be the most active compounds of the series with IC50 value for antibacterial in the range 0.39 to 0.75 μM/mL. Furthermore, the in vitro cytotoxic potential of the compounds was appraised by hemolytic assay. The results showed that some of the synthesized compounds exhibited marked activity.
Agrawal, Ram Kishore,Dighade, Sachin J.,Dwivedi, Deepak K.,Sahu, Adarsh
(2020/02/04)

Preclinical evaluation of 1,2,4-triazole-based compounds targeting voltage-gated sodium channels (VGSCs) as promising anticonvulsant drug candidates
Epilepsy is a chronic neurological disorder affecting nearly 65–70 million people worldwide. Despite the observed advances in the development of new antiepileptic drugs (AEDs), still about 30–40% of patients cannot achieve a satisfactory seizure control. In our current research, we aimed at using the combined results of radioligand binding experiments, PAMPA-BBB assay and animal experimentations in order to design a group of compounds that exhibit broad spectrum of anticonvulsant activity. The synthesized 4-alkyl-5-substituted-1,2,4-triazole-3-thione derivatives were primarily screened in the maximal electroshock-induced seizure (MES) test in mice. Next, the most promising compounds (17, 22) were investigated in 6 Hz (32 mA) psychomotor seizure model. Protective effect of compound 22 was almost similar to that of levetiracetam. Moreover, these compounds did not induce genotoxic and hemolytic changes in human cells as well as they were characterized by low cellular toxicity. Taking into account the structural requirements for good anticonvulsant activity of 4-alkyl-5-aryl-1,2,4-triazole-3-thiones, it is visible that small electron-withdrawing substituents attached to phenyl ring have beneficial effects both on affinity towards VGSCs and protective activity in the animal models of epilepsy.
Kaproń, Barbara,?uszczki, Jarogniew J.,Siwek, Agata,Karcz, Tadeusz,Nowak, Gabriel,Zagaja, Miros?aw,Andres-Mach, Marta,Stasi?owicz, Anna,Cielecka-Piontek, Judyta,Kocki, Janusz,Plech, Tomasz
(2019/11/13)

Design, synthesis, and in vitro evaluation of novel 1,3,4-oxadiazolecarbamothioate derivatives of Rivastigmine as selective inhibitors of BuChE
Rivastigmine has been prescribed for the therapy of Alzheimer’s disease (AD) symptoms. This drug is classified in the carbamate derivative group that has dual activity against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). According to the structure of Rivastigmine and its performance, a new series of 5-aryl-1,3,4-oxadiazole-2-carbamothioate compounds I–XI was synthesized using structure-based drug discovery approaches. For this purpose a set of these compounds were designed with computational docking method and their interactions with amino acid residues in the active sites of AChE and BuChE checked out. The structures of synthesized compounds were established by physicochemical and spectroscopic methods. The carbamoyl moiety of Rivastigmine structure was modified to carbamothioate and the effects of 1,3,4-oxadiazole heterocycle as a pharmacophoric nucleus were investigated. The potential of the synthesized compounds I–XI was evaluated against two most known agents of AD (AChE and BuChE) to determine their IC50 values. The results of the docking showed the range of binding affinity for the best poses of ten individual conformers for any compounds (I–XI) was between ?7.81 (VI) and ?6.75 (II) kcal/mol. The results of biological experiments displayed that most synthetic compounds (I–VIII) showed moderate to excellent selective activity range against BuChE (0.51–69.44 μM). In vitro cytotoxicity evaluation of these compounds (I–XI) by MTT assay on human dermal fibroblast (HDF) cell line exhibited no activity against HDF. The compound VI [S-(5-(p-tolyl)-1,3,4-oxadiazol-2-yl) ethyl(methyl)carbamothioate] showed the most stable binding affinity (?7.81 kcal/mol) and the lowest IC50 value (0.51 μM) in comparison with Rivastigmine with 7.72 μM and Donepezil with 5.20 μM against BuChE.
Fallah, Akram,Mohanazadeh, Farajollah,Safavi, Maliheh
p. 341 - 355
(2019/12/30)

Modulation of estrogen-related receptors subtype selectivity: Conversion of an ERRβ/γ selective agonist to ERRα/β/γ pan agonists
Estrogen Related Receptors (ERRs) are key regulators of energy homeostasis and play important role in the etiology of metabolic disorders, skeletal muscle related disorders, and neurodegenerative diseases. Among the three ERR isoforms, ERRα emerged as a potential drug target for metabolic and neurodegenerative diseases. Although ERRβ/γ selective agonist chemical tools have been identified, there are no chemical tools that effectively target ERRα agonism. We successfully engineered high affinity ERRα agonism into a chemical scaffold that displays selective ERRβ/γ agonist activity (GSK4716), providing novel ERRα/β/γ pan agonists that can be used as tools to probe the physiological roles of these nuclear receptors. We identified the structural requirements to enhance selectivity toward ERRα. Molecular modeling shows that our novel modulators have favorable binding modes in the LBP of ERRα and can induce conformational changes where Phe328 that originally occupies the pocket is dislocated to accommodate the ligands in a rather small cavity. The best agonists up-regulated the expression of target genes PGC-1α and PGC-1β, which are necessary to achieve maximal mitochondrial biogenesis. Moreover, they increased the mRNA levels of PDK4, which play an important role in energy homeostasis.
Avdagic, Amer,Billon, Cyrielle,Burris, Sheryl L.,Burris, Thomas P.,Elagawany, Mohamed,Elgendy, Bahaa,Goher, Shaimaa S.,Hegazy, Lamees,Sanders, Ryan,Shahien, Mohamed,Sitaula, Sadichha
(2020/07/21)

COMPOUNDS COMPRISING CLEAVABLE LINKER AND USES THEREOF
Provided are a compound including a cleavable linker, a use thereof, and an intermediate compound for preparing the same, and more particularly, the compound including a cleavable linker of the present invention may include an active agent (for example, a drug, a toxin, a ligand, a probe for detection, etc.) having a specific function or activity, a SO2 functional group which is capable of selectively releasing the active agent, and a functional group which triggers a chemical reaction, a physicochemical reaction and/or a biological reaction by external stimulation, and may further include a ligand (for example, oligopeptide, polypeptide, antibody, etc.) having binding specificity for a desired target receptor.
-
Page/Page column 174-175

(2020/07/21)

COMPOUNDS COMPRISING CLEAVABLE LINKER AND USES THEREOF
Provided are a compound including a cleavable linker, a use thereof, and an intermediate compound for preparing the same, and more particularly, the compound including a cleavable linker of the present invention may include an active agent (for example, a drug, a toxin, a ligand, a probe for detection, etc.) having a specific function or activity, a -S(=0)(=N-)- functional group which is capable of selectively releasing the active agent, and a functional group which triggers a chemical reaction, a physicochemical reaction and/or a biological reaction by external stimulation, and may further include a ligand (for example, oligopeptide, polypeptide, antibody, etc.) having binding specificity for a desired target receptor.
-
Page/Page column 165

(2020/09/03)

Efficient Synthesis of 1,4-Bis(5-aryl-1,3,4-oxadiazol-2-yl)-2,3,5,6-tetrafluorobenzenes
Abstract: An efficient acid-catalyzed condensation between substituted benzohydrazides and 2,3,5,6-tetrafluoroterephthalic acid to form 1,4-bis(5-aryl-1,3,4-oxadiazol-2-yl)-2,3,5,6-tetrafluorobenzenes is reported. The products were isolated in 74–87% yield and were characterized by 1H NMR, IR, and mass spectra.
Dhotre, B. K.,Khandebharad, A. U.,Pathan, A.,Raut, S. V.
p. 1324 - 1326
(2020/10/02)

Synthesis of isoquinolones by visible-light-induced deaminative [4+2] annulation reactions
Herein a metal-free approach for the synthesis of isoquinolone derivatives by means of photoinitiated deaminative [4+2] annulation of alkynes and N-amidepyridinium salts is described. This protocol exhibits a broad scope and good functional group tolerance and regioselectivity under benign reaction conditions. Preliminary studies suggest that the critical amide radical is derived from the photocatalytic cleavage of the N-N bond of the N-amidepyridinium salt, which adds to the triple bond of the alkyne and undergoes the annulation process to afford the desired isoquinolones.
Zhao, Yating,Shi, Chengcheng,Su, Xing,Xia, Wujiong
supporting information
p. 5259 - 5262
(2020/07/30)

Design, Synthesis, and Pharmacological Evaluation of First-in-Class Multitarget N-Acylhydrazone Derivatives as Selective HDAC6/8 and PI3Kα Inhibitors
Targeting histone deacetylases (HDACs) and phosphatidylinositol 3-kinases (PI3Ks) is a very promising approach for cancer treatment. This manuscript describes the design, synthesis, in vitro pharmacological profile, and molecular modeling of a novel class of N-acylhydrazone (NAH) derivatives that act as HDAC6/8 and PI3Kα dual inhibitors. The surprising selectivity for PI3Kα may be related to differences in the conformation in the active site. Cellular studies showed that these compounds act in HDAC6 inhibition and the PI3/K/AKT/mTOR pathway. The compounds that are selective for inhibition of HDAC6/8 and inhibit PI3Kα show potential for the treatment of cancer.
Alves, Marina A.,Chaves, Lorrane S.,Fernandes, Patrícia D.,Fraga, Carlos A. M.,Guerra, Fabiana S.,Rodrigues, Daniel A.,Sagrillo, Fernanda S.,Sant'Anna, Carlos M. R.,Thota, Sreekanth,de Sena M. Pinheiro, Pedro
supporting information

(2020/02/25)

Structure-based design, synthesis, biological evaluation and molecular docking study of 4-hydroxy-n'-methylenebenzohydrazide derivatives acting as tyrosinase inhibitors as potentiate anti-melanogenesis activities
Background: Melanogenesis is a process of melanin synthesis, which is a primary response for the pigmentation of human skin. Tyrosinase is a key enzyme, which catalyzes a rate-limiting step of the melanin formation. Natural products have shown potent inhibitors, but some of these possess toxicity. Numerous synthetic inhibitors have been developed in recent years may lead to the potent anti– tyrosinase agents. Objective: A number of 4-hydroxy-N'-methylenebenzohydrazide analogues with related structure to chalcone and tyrosine were constructed with various substituents at the benzyl ring of the mole-cule and evaluate as a tyrosinase inhibitor. In addition, computational analysis and metal chelating potential have been evaluated. Method: Design and synthesized compounds were evaluated for activity against mushroom ty-rosinase. The metal chelating capacity of the potent compound was examined using the mole ratio method. Molecular docking of the synthesized compounds was carried out into the tyrosine active site. Result: Novel 4-hydroxy-N'-methylenebenzohydrazide derivatives were synthesized. The two compounds 4c and 4g showed an IC50 near the positive control, led to a drastic inhibition of ty-rosinase. Confirming in vitro results were performed via the molecular docking analysis demon-strating hydrogen bound interactions of potent compounds with histatidine-Cu+2 residues with in the active site. Kinetic study of compound 4g showed competitive inhibition towards tyrosinase. Metal chelating assay indicates the mole fraction of 1:2 stoichiometry of the 4g-Cu2+ complex. Conclusion: The findings in the present study demonstrate that 4-Hydroxy-N'-methylenebenzohydrazide scaffold could be regarded as a bioactive core inhibitor of tyrosinase and can be used as an inspiration for further studies in this area.
Iraji, Aida,Khoshneviszadeh, Mahsima,Bakhshizadeh, Pegah,Edraki, Najmeh,Khoshneviszadeh, Mehdi
p. 892 - 902
(2020/08/19)

Green synthesis of benzamide-dioxoisoindoline derivatives and assessment of their radical scavenging activity – Experimental and theoretical approach
A series of benzamide-dioxoisoindoline derivatives 3 was obtained, starting from phthalic anhydride and different benzoyl hydrazides 2, by ultrasound irradiation in water as solvent and without any catalyst. Five obtained compounds have been reported in this study for the first time and crystal structure of compound 3h was determined. All compounds were subjected to experimental determination of their antioxidative potential. DPPH test revealed that newly synthesized phenolic compounds 3d, 3e, and 3j are the best antioxidants. Additionally, probable radical scavenging pathway was analysed for reactions of the most active compounds and some radicals that can be found in living cells.
Bogdanovi?, Goran A.,Milovanovi?, Vesna M.,Novakovi?, Sla?ana,Petrovi?, Vladimir P.,Petrovi?, Zorica D.,Simijonovi?, Du?ica
(2020/08/19)

Design, synthesis and biological evaluation of 2-(phenoxymethyl)-5-phenyl-1,3,4-oxadiazole derivatives as anti-breast cancer agents
Structural based molecular docking approach revealed the findings of 2-(phenoxymethyl) -5-phenyl-1,3,4-oxadiazole derivatives. The compounds (7a-o) were synthesized and characterized well by using conventional methods. The compounds, 7b and 7m were reconfirmed through single crystal XRD analysis. The synthesized compounds (7a-o) were evaluated their antiproliferative activities against MCF-7 and MDA-MB-453. Furthermore, Lipinski's rule of five and pharmacokinetic properties were predicted for the test compounds. These results demonstrate that the compounds 7b and 7d exhibit more potent cytotoxicity and 7d exhibits dose-dependent activity and reduced cell viability. Further, the mechanism of action for the induced apoptosis was observed through morphological changes and western blotting analysis. These findings may furnish the lead for further development.
Lakshmithendral,Saravanan,Elancheran,Archana,Manikandan,Arjun,Ramanathan,Lokanath,Kabilan
p. 1 - 10
(2019/02/25)

Synthesis and antimicrobial activity of piperine analogues containing 1,2,4-triazole ring
A series 1,2,4-triazole piperine analogues (TP1-TP6) were designed and synthesized. The structures were confirmed using 1H NMR and 13C NMR. Antibacterial study was done using Gram-positive (Staphylococcus aureus and Bacillus cereus) and Gram-negative microorganisms (E. coli and Pseudomonas aeruginosa) by disc diffusion method. Compound containing chloro substitution (TP6) showed the highest effect, while compound TP1, TP3, TP4, TP5 showed the moderate activity.
Kumar, Kottakki Naveen,Amperayani, Karteek Rao,Ummdi, V. Ravi Sankar,Parimi, Uma Devi
p. 1077 - 1080
(2019/04/05)

Targeting malaria and leishmaniasis: Synthesis and pharmacological evaluation of novel pyrazole-1,3,4-oxadiazole hybrids. Part II
In continuance with earlier reported work, an extension has been carried out by the same research group. Mulling over the ongoing condition of resistance to existing antimalarial agents, we had reported synthesis and antimalarial activity of certain pyrazole-1,3,4-oxadiazole hybrid compounds. Bearing previous results in mind, our research group ideated to design and synthesize some more derivatives with varied substitutions of acetophenone and hydrazide. Following this, derivatives 5a–r were synthesized and tested for antimalarial efficacy by schizont maturation inhibition assay. Further, depending on the literature support and results of our previous series, certain potent compounds (5f, 5n and 5r) were subjected to Falcipain-2 inhibitory assay. Results obtained for these particular compounds further strengthened our hypothesis. Here, in this series, compound 5f having unsubstituted acetophenone part and a furan moiety linked to oxadiazole ring emerged as the most potent compound and results were found to be comparable to that of the most potent compound (indole bearing) of previous series. Additionally, depending on the available literature, compounds (5a–r) were tested for their antileishmanial potential. Compounds 5a, 5c and 5r demonstrated dose-dependent killing of the promastigotes. Their IC50 values were found to be 33.3 ± 1.68, 40.1 ± 1.0 and 19.0 ± 1.47 μg/mL respectively. These compounds (5a, 5c and 5r) also had effects on amastigote infectivity with IC50 of 44.2 ± 2.72, 66.8 ± 2.05 and 73.1 ± 1.69 μg/mL respectively. Further target validation was done using molecular docking studies. Acute oral toxicity studies for most active compounds were also performed.
Verma, Garima,Khan, Mohemmed Faraz,Mohan Nainwal, Lalit,Ishaq, Mohd,Akhter, Mymoona,Bakht, Afroz,Anwer, Tariq,Afrin, Farhat,Islamuddin, Mohammad,Husain, Ibraheem,Alam, Mohammad Mumtaz,Shaquiquzzaman, Mohammad
(2019/05/29)

Synthesis, characterisation of new derivatives with mono ring system of 1,2,4-triazole scaffold and their anticancer activities
In the present study, two important starting materials and 18 new 1,2,4-triazole compounds with mono ring system have been synthesized and characterized. The mono system showed 16 compounds of a Schiff base moiety attached to the triazole ring which was prepared from the corresponding starting material 5(A–B) or piperidinium salt system 6(A–B). All these compounds were characterized using Fourier Transform Infrared (FT-IR) and Nuclear Magnetic Resonance (NMR) spectroscopy and carbon hydrogen nitrogen (CHN) elemental analysis. The compounds were selected for in vitro anticancer study to test the therapeutic cytotoxic potential against cancer cells. The MTT test was conducted against human breast (MCF-7) and colorectal (HCT-116) cancer cells. Among all the compounds tested, 7A-i demonstrated more pronounced in vitro anticancer effect against MCF-7 and HCT-116 cells with IC50 of 38 and 19.2 μM, respectively, comparable to that of the standard reference drugs, tamoxifen and 5-fluorouracil, respectively. Compound 7A-vi showed a considerable cytotoxic effect with IC50 53 and 41.2 μM against MCF-7 and HCT-116 cells, respectively. Compounds 7A-ii, 7A-iii and 7A-v exhibited moderate cytotoxicity with IC50 68, 91 and 85 μM, respectively against MCF-7 cells and also 59.3, 81.7 and 137.1 μM against HCT-116 cells, respectively. However, all other compounds tested in this study showed poor cytotoxicity against both the cell lines. Cellular morphological analysis revealed that the cytotoxicity induced by the compounds could probably due to autophagy. It can be concluded that 1,2,4-triazole derivatives can be promising therapeutic agents. Further studies will be done to investigate the antitumor efficacy of the 1,2,4-triazole derivatives using suitable preclinical models.
Slaihim, Mukhlif Mohsin,Al-Suede, Fouad Saleih R.,Khairuddean, Melati,Khadeer Ahamed, Mohamed B.,Shah Abdul Majid, Amin Malik
p. 78 - 87
(2019/06/27)

NOVEL BENZODIAZEPINE DERIVATIVES AND USES THEREOF
The present disclosure provides compounds and compositions capable of extending lifespan, and methods of use thereof.
-
Paragraph 0738-0740

(2019/12/24)

COMPOUNDS COMPRISING CLEAVABLE LINKER AND USES THEREOF
Provided are a compound including a cleavable linker, a use thereof, and an intermediate compound for preparing the same, and more particularly, the compound including a cleavable linker of the present invention may include an active agent (for example, a drug, a toxin, a ligand, a probe for detection, etc.) having a specific function or activity, a SO2 functional group which is capable of selectively releasing the active agent, and a functional group which triggers a chemical reaction, a physicochemical reaction and/or a biological reaction by external stimulation, and may further include a ligand (for example, oligopeptide, polypeptide, antibody, etc.) having binding specificity for a desired target receptor.
-
Page/Page column 179; 180

(2019/01/21)

Dithiocarbamate as a valuable scaffold for the inhibition of metallo-β-lactmases
The ‘superbug’ infection caused by metallo-β-lactamases (MβLs) has grown into an emergent health threat. Given the clinical importance of MβLs, a novel scaffold, dithiocarbamate, was constructed. The obtained molecules, DC1, DC8 and DC10, inhibited MβLs NDM-1, VIM-2, IMP-1, ImiS and L1 from all three subclasses, exhibiting an IC50 50 0.22 μM). DC1-2, DC4, DC8 and DC10 restored antimicrobial effects of cefazolin and imipenem against E. coli-BL21, producing NDM-1, ImiS or L1, and DC1 showed the best inhibition of E. coli cells, expressing the three MβLs, resulting in a 2-16-fold reduction in the minimum inhibitory concentrations (MICs) of both antibiotics. Kinetics and isothermal titration calorimetry (ITC) assays showed that DC1 exhibited a reversible, and partially mixed inhibition, of NDM-1, ImiS and L1, with Ki values of 0.29, 0.14 and 5.06 μM, respectively. Docking studies suggest that the hydroxyl and carbonyl groups of DC1 form coordinate bonds with the Zn (II) ions, in the active center of NDM-1, ImiS and L1, thereby inhibiting the activity of the enzymes. Cytotoxicity assays showed that DC1, DC3, DC7 and DC9 have low toxicity in L929 mouse fibroblastic cells, at a dose of up to 250 μM. These studies revealed that the dithiocarbamate is a valuable scaffold for the development of MβLs inhibitors.
Ge, Ying,Xu, Li-Wei,Liu, Ya,Sun, Le-Yun,Gao, Han,Li, Jia-Qi,Yang, Kewu
(2019/11/20)

Synthesis and antitumor evaluation of novel fused heterocyclic 1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole derivatives
In this study, twenty three 3,6-disubstituted 1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole derivatives were synthesized and their antiproliferative activities in vitro were studied against SMMC-7721, HeLa, A549, and L929 by the CCK-8 assay. The bioassay results demonstrated that all tested compounds 8(a–w) exhibited antiproliferation with different degrees, and some compounds showed better effects than reference drug 5-fluorouracil. Among these screened compounds, compounds 8a, 8d, and 8l displayed significant antitumor activities in inhibiting SMMC-7721cell proliferation with IC50 values of 1.64, 1.74, and 1.61 μM, respectively. Compounds 8d and 8l were manifested highly effective biological activity versus HeLa cells with IC50 values of 2.23 and 2.84 μM, respectively. Compound 8l was found to have the highest antitumor potency against A549 cells with IC50 value of 2.67 μM. Furthermore, all compounds exhibited weaker cytotoxic effects than 5-fluorouracil on normal cell lines L929.
Liu, Xiao-Jia,Liu, Hai-Ying,Wang, Hai-Xin,Shi, Yan-Ping,Tang, Rui,Zhang, Shuai,Chen, Bao-Quan
p. 1718 - 1725
(2019/08/02)

Structural design, synthesis and substituent effect of hydrazone-N-acylhydrazones reveal potent immunomodulatory agents
4-(Nitrophenyl)hydrazone derivatives of N-acylhydrazone were synthesized and screened for suppress lymphocyte proliferation and nitrite inhibition in macrophages. Compared to an unsubstituted N-acylhydrazone, active compounds were identified within initial series when hydroxyl, chloride and nitro substituents were employed. Structure-activity relationship was further developed by varying the position of these substituents as well as attaching structurally-related substituents. Changing substituent position revealed a more promising compound series of anti-inflammatory agents. In contrast, an N-methyl group appended to the 4-(nitrophenyl)hydrazone moiety reduced activity. Anti-inflammatory activity of compounds is achieved by modulating IL-1β secretion and prostaglandin E2 synthesis in macrophages and by inhibiting calcineurin phosphatase activity in lymphocytes. Compound SintMed65 was advanced into an acute model of peritonitis in mice, where it inhibited the neutrophil infiltration after being orally administered. In summary, we demonstrated in great details the structural requirements and the underlying mechanism for anti-inflammatory activity of a new family of hydrazone-N-acylhydrazone, which may represent a valuable medicinal chemistry direction for the anti-inflammatory drug development in general.
Meira, Cássio S.,dos Santos Filho, José Maurício,Sousa, Caroline C.,Anjos, Pamela S.,Cerqueira, Jéssica V.,Dias Neto, Humberto A.,da Silveira, Rafael G.,Russo, Helena M.,Wolfender, Jean-Luc,Queiroz, Emerson F.,Moreira, Diogo R.M.,Soares, Milena B.P.
p. 1971 - 1985
(2018/03/12)

Acetophenone benzoylhydrazones as antioxidant agents: Synthesis, in vitro evaluation and structure-activity relationship studies
Acetophenone and its analogues are naturally-occurring compounds found in many foods and plants. In this study, a series of acetophenone benzoylhydrazones 5a-o were designed and synthesized as new potential antioxidant agents. Designed molecules contain hydrazone and phenolic hydroxyl moieties which possibly contribute to antioxidant activity. The antioxidant properties of compounds 5a-o in terms of reducing ability and radical-scavenging activity were assessed by using FRAP and DPPH tests, respectively. While the unsubstituted compound 5a had the superior capacity in the FRAP assay, the 2,4-dihydroxyacetophenone analogue 5g was the most potent radical scavenger in the DPPH method. The antioxidant potential of representative compounds 5a and 5g was further confirmed by TEAC and ORAC assays. Cell viability assays revealed that while the promising compounds 5a and 5g had no significant toxicity against HepG2 and NIH3T3 cells, they potently protected HepG2 cells against H2O2-induced oxidative damage at low concentrations. Furthermore, spectroscopic studies with different biometals demonstrated that 5g was able to interact with Cu2+ to form a 1:1 complex.
Emami, Saeed,Esmaili, Zahra,Dehghan, Gholamreza,Bahmani, Maryam,Hashemi, Seyedeh Mahdieh,Mirzaei, Hassan,Shokrzadeh, Mohammad,Moradi, Seyed Ershad
p. 292 - 299
(2018/06/29)

N-(5-Methyl-1,3-Thiazol-2-yl)-2-{[5-((Un)Substituted- Phenyl)1,3,4-Oxadiazol-2-yl]Sulfanyl}acetamides. Unique Biheterocycles as Promising Therapeutic Agents
An electrophile, 2-bromo-N-(5-methyl-1,3-thiazol-2-yl)acetamide, was synthesized by the reaction of 5-methyl-1,3-thiazol-2-amine and bromoacetyl bromide in an aqueous medium. In a parallel scheme, a series of (un)substituted benzoic acids was converted sequentially into respective esters, acid hydrazides, and then into 1,3,4-oxadiazole heterocyclic cores. The electrophile was coupled with the aforementioned 1,3,4-oxadiazoles to obtain the targeted bi-heterocyles. Structural analysis of the synthesized compounds was performed by IR, EI-MS, 1H NMR, and 13C NMR. The enzyme inhibition study of these molecules was carried out against four enzymes, namely, acetylcholinesterase, butyrylcholinesterase, α-glucosidase, and urease. The interactions of these compounds with respective enzymes were recognized by their in silico study. Moreover, their cytotoxicity was also determined to find out their utility as possible therapeutic agents.
Abbasi,Ramzan,Aziz-ur-Rehman,Siddiqui,Shah,Hassan,Seo,Ashraf,Mirza,Ismail
p. 801 - 811
(2019/02/27)

Microwave assisted synthesis and evaluation of some substituted 1,3,4-oxadiazoles as free radical scavenger
A series of 5-(4-substituted phenyl)-1,3,4-oxadiazoles (4a-h) were prepared from 4-substituted benzoic acid hydrazides (3a-h). Structures of the synthesized compounds were confirmed on the basis of IR, 13C NMR, Mass spectral methods and elemental analysis. The compounds were screened for antioxidant activities using hydrogen peroxide scavenging method comparing with ascorbic acid as standard antioxidant. The results reveal that the compounds possess significant free radical scavenging activities. It is recommended that these compounds might be used in future to generate derivatives for emerging free radical scavenger.
Upadhyay, Prabhat Kumar,Mishra, Pradeep
p. 661 - 666
(2020/07/02)

3. 6 - Disubstituted [1, 2, 4] triazolo [3, 4 - b] [1, 3, 4] thiadiazole compound and use thereof
The invention discloses 3,6-disubstituted[1,2,4]triazolyl[3,4-b][1,3,4]thiadiazole compounds represented by general formula (I), and pharmaceutically acceptable salts or pharmaceutically acceptable solvates thereof. The compounds can be used as a transpeptidase SrtA inhibitor of Staphylococcus aureus, Bacillus pyogenes, Bacillus anthracis, Streptococcus pneumoniae and other Gram-positive bacteria, and can be used to prepare drugs for treating pathogen infection diseases with the transpeptidase SrtA of the Gram-positive bacteria, such as Staphylococcus aureus, Bacillus pyogenes, Bacillus anthracis and Streptococcus pneumoniae as target. The compounds avoid selection pressure induced drug resistance of pathogens to a certain degree, and mitigate threat of continuous drug-resistant pathogens to the health of human.
-
Paragraph 0065

(2018/11/22)

Design and synthesis of tailored human caseinolytic protease P inhibitors
Human caseinolytic protease P (hClpP) is important for degradation of misfolded proteins in the mitochondrial unfolded protein response. We here introduce tailored hClpP inhibitors that utilize a steric discrimination in their core naphthofuran scaffold to selectively address the human enzyme. This novel inhibitor generation exhibited superior activity compared to previously introduced beta-lactones, optimized for bacterial ClpP. Further insights into the bioactivity and binding to cellular targets were obtained via chemical proteomics as well as proliferation- and migration studies in cancer cells.
Gronauer, Thomas F.,Mandl, Melanie M.,Lakemeyer, Markus,Hackl, Mathias W.,Me?ner, Martina,Korotkov, Vadim S.,Pachmayr, Johanna,Sieber, Stephan A.
supporting information
p. 9833 - 9836
(2018/09/10)

1-(2-Hydroxybenzoyl)-thiosemicarbazides are promising antimicrobial agents targeting D-alanine-D-alanine ligase in bacterio
The bacterial cell wall and the enzymes involved in peptidoglycan synthesis are privileged targets for the development of novel antibacterial agents. In this work, a series of 1-(2-hydroxybenzoyl)-thiosemicarbazides inhibitors of D-Ala-D-Ala ligase (Ddl) were designed and synthesized in order to target resistant strains of bacteria. Among these, the 4-(3,4-dichlorophenyl)-1-(2-hydroxybenzoyl)-3-thiosemicarbazide 29 was identified as a potent Ddl inhibitor with activity in the micromolar range. This compound, possessing strong antimicrobial activity including against multidrug resistant strains, was proven to act through a bactericidal mechanism and demonstrated very low cytotoxicity on THP-1 human monocytic cell line. Inhibition of Ddl activity by 29 was confirmed in bacterio using UPLC-MS/MS by demonstrating an increase in D-Ala intracellular pools accompanied by a commensurate decrease in D-Ala-D-Ala. Further structure-activity relationships (SARs) studies provided evidence that the hydroxyl substituent in the 2-position (R1) of the benzoylthiosemicarbazide scaffold is essential for the enzymatic inhibition. This work thus highlights the 1-(2-hydroxybenzoyl)-thiosemicarbazide motif as a very promising tool for the development of novel antibacterial compounds acting through an interesting mechanism of action and low cytotoxicity.
Ameryckx, Alice,Thabault, Léopold,Pochet, Lionel,Leimanis, Serge,Poupaert, Jacques H.,Wouters, Johan,Joris, Bernard,Van Bambeke, Fran?oise,Frédérick, Rapha?l
supporting information
p. 324 - 338
(2018/10/15)

Design, synthesis, and evaluation of simple phenol amides as ERRγ agonists
Herein we report the design and synthesis of a series of simple phenol amide ERRγ agonists based on a hydrazone lead molecule. Our structure activity relationship studies in this series revealed the phenol portion of the molecule to be required for activity. Attempts to replace the hydrazone with more suitable chemotypes led to a simple amide as a viable alternative. Differential hydrogen-deuterium exchange experiments were used to help understand the structural basis for binding to ERRγ and aid in the development of more potent ligands.
Lin, Hua,Doebelin, Christelle,Patouret, Rémi,Garcia-Ordonez, Ruben D.,Ra Chang, Mi,Dharmarajan, Venkatasubramanian,Bayona, Claudia Ruiz,Cameron, Michael D.,Griffin, Patrick R.,Kamenecka, Theodore M.
p. 1313 - 1319
(2018/03/21)

A 4 - hydroxy -2 ' - (5 - nitrofuran easy to be) - benzoyl jing synthetic method (by machine translation)
The invention discloses a 4 - hydroxy - 2' - (5 - nitrofuran easy to be) - benzoyl jing synthetic method. The method of the invention is hydroxy benzoic acid methyl ester will, hydrazine hydrate in ethanol aqueous solution in the hydrazinolysis, to obtain hydroxy benzoyl jing, then the hydroxy benzoyl jing with 5 - nitro furfural in dilute sulfuric acid catalytic under 50 - 90 °C reaction 1 - 3 hours, prepared by the condensation of 4 - hydroxy - 2' - (5 - nitrofuran easy to be) - [...]. The present invention provides a hydroxy benzoyl jingjing in the aqueous phase in a one-step synthesis of 4 - hydroxy - 2' - (5 - nitrofuran easy to be) - benzoyl jing method, the traditional pyridine solvent has handles improved, improves the product purity and yield, completely avoiding pollution of the pyridine solvent. (by machine translation)
-
Paragraph 0023; 0025-0026

(2019/01/10)

Synthesis of novel 5-(aroylhydrazinocarbonyl)escitalopram as cholinesterase inhibitors
A novel series of 5-(aroylhydrazinocarbonyl)escitalopram (58–84) have been designed, synthesized and tested for their inhibitory potential against cholinesterases. 3-Chlorobenzoyl- (71) was found to be the most potent compound of this series having IC50 1.80 ± 0.11 μM for acetylcholinesterase (AChE) inhibition. For the butyrylcholinesterase (BChE) inhibition, 2-bromobenzoyl- (76) was the most active compound of the series with IC50 2.11 ± 0.31 μM. Structure-activity relationship illustrated that mild electron donating groups enhanced enzyme inhibition while electron withdrawing groups reduced the inhibition except o-NO2. However, size and position of the substituents affected enzyme inhibitions.. In docking study of AChE, the ligands 71, 72 and 76 showed the scores of 5874, 5756 and 5666 and ACE of ?64.92,-203.25 and ?140.29 kcal/mol, respectively. In case of BChE, ligands 71, 76 and 81 depicted high scores 6016, 6150 and 5994 with ACE values ?170.91, ?256.84 and ?235.97 kcal/mol, respectively.
Nisa, Mehr-un,Munawar, Munawar A.,Iqbal, Amber,Ahmed, Asrar,Ashraf, Muhammad,Gardener, Qurra-tul-Ann A.,Khan, Misbahul A.
supporting information
p. 396 - 406
(2017/07/10)

Design and optimization of N-acylhydrazone pyrimidine derivatives as E. coli PDHc E1 inhibitors: Structure-activity relationship analysis, biological evaluation and molecular docking study
By targeting the thiamin diphosphate (ThDP) binding site of Escherichia coli (E. coli) pyruvate dehydrogenase multienzyme complex E1 (PDHc E1), a series of novel ‘open-chain’ classes of ThDP analogs A, B, and C with N-acylhydrazone moieties was designed and synthesized to explore their activities against E. coli PHDc E1 in vitro and their inhibitory activity against microbial diseases were further evaluated in vivo. As a result, A1–23 exhibited moderate to potent inhibitory activities against E. coli PDHc E1 (IC50 = 0.15–23.55 μM). The potent inhibitors A13, A14, A15, C2, had strong inhibitory activities with IC50 values of 0.60, 0.15, 0.39 and 0.34 μM against E. coli PDHc E1 and with good enzyme-selective inhibition between microorganisms and mammals. Especially, the most powerful inhibitor A14 could 99.37% control Xanthimonas oryzae pv. Oryzae. Furthermore, the binding features of compound A14 within E. coli PDHc E1 were investigated to provide useful insights for the further construction of new inhibitor by molecular docking, site-directed mutagenesis, and enzymatic assays. The results indicated that A14 had most powerful inhibition against E. coli PDHc E1 due to the establishment of stronger interaction with Glu571, Met194, Glu522, Leu264 and Phe602 at active site of E.coli PDHc E1. It could be used as a lead compound for further optimization, and may have potential as a new microbicide.
He, Haifeng,Xia, Hongying,Xia, Qin,Ren, Yanliang,He, Hongwu
p. 5652 - 5661
(2017/10/09)

New Biguanides as Anti-Diabetic Agents, Part II: Synthesis and Anti-Diabetic Properties Evaluation of 1-Arylamidebiguanide Derivatives as Agents of Insulin Resistant Type II Diabetes
New 1-arylamidebiguanide hydrochloride salts were synthesized via reaction of hydrazide derivatives with dicyandiamide in acidic medium. The structure of the obtained derivatives was characterized by spectroscopic and elemental analysis tools. The anti-diabetic properties of the synthesized compounds were determined. Oral treatment of hyperglycemic rats with the synthesized biguanide derivatives showed a significant decrease of the elevated glucose in comparison with the anti-diabetic standard drug, metformin. The effects of the synthesized biguanide derivatives on the diabetic properties regarding liver function enzyme activities (AST, ALT, and ALP), lipid profiles (TC, TG, and TL), lipid peroxide, and nitrous oxide as well as histopathological characteristics were investigated and discussed.
Basyouni, Wahid M.,Abbas, Samir Y.,El Shehry, Mohamed F.,El-Bayouki, Khairy A.M.,Aly, Hanan F.,Arafa, Azza,Soliman, Mahmoud S.
(2017/10/23)

Synthesis and pharmacological screening: Sulfa derivatives of 2-pipecoline-bearing 1,3,4-oxadiazole core
An electrophile, 1-(4-(bromomethylbenzenesulfonyl)-2-methylpiperidine, was synthesized by the reaction of 2-methylpiperidine (2-pipecoline) and 4-bromomethylbenzenesulfonyl chloride in a weak basic medium under pH control. A series of nucleophiles, 5-aryl/aralkyl-1,3,4-oxadiazol-2-thiols, were synthesized from corresponding carboxylic acids in three steps. The title molecules were synthesized by coupling the electrophile to nucleophiles in an aprotic medium using LiH as an activator. The structures of all synthesized compounds were corroborated through IR, 1H NMR, and EI-MS techniques. All the compounds were screened for their pharmacological behavior, particularly, antibacterial and enzyme inhibitory activities. Notably efficient results were obtained against both gram-positive and gram-negative bacterial strains. Regarding enzyme inhibition, compounds were efficient against acetylcholinesterase and butyrylcholinesterase.
Aziz-ur-Rehman,Arif,Abbasi,Siddiqui,Rasool,Shah
p. 328 - 339
(2017/07/04)

Pyridyl-Acyl Hydrazone Rotaxanes and Molecular Shuttles
We report on rotaxanes featuring a pyridyl-acyl hydrazone moiety on the axle as a photo/thermal-switchable macrocycle binding site. The pyridyl-acyl E-hydrazone acts as a hydrogen bonding template that directs the assembly of a benzylic amide macrocycle around the axle to form [2]rotaxanes in up to 85% yield; the corresponding Z-hydrazone thread affords no rotaxane under similar conditions. However, the E-rotaxane can be smoothly converted into the Z-rotaxane in 98% yield under UV irradiation. The X-ray crystal structures of the E- and Z-rotaxanes show different intercomponent hydrogen bonding patterns. In molecular shuttles containing pyridyl-acyl hydrazone and succinic amide ester binding sites, the change of position of the macrocycle on the thread can be achieved through a series of light irradiation and heating cycles with excellent positional integrity (>95%) and switching fidelity (98%) in each state.
Leigh, David A.,Marcos, Vanesa,Nalbantoglu, Tugrul,Vitorica-Yrezabal, I?igo J.,Yasar, F. Tuba,Zhu, Xiaokang
supporting information
p. 7104 - 7109
(2017/05/31)

Synthesis of N’-(2-methoxybenzylidene)-4-hydroxy benzohydrazide and N’-(4-nitrobenzylidene)-4-hydroxy benzohydrazide, in silico study and antibacterial activity
In this study, synthesized N'-(2-methoxybenzylidene)-4-hydroxybenzohydrazide and N'-(4-nitrobenzylidene)-4-hydroxybenzohydrazide in two step reaction by using methylparaben as starting material has been performed. Methylparaben was treated with hydrazine hydrate to obtain 4-hydroxybenzohydrazide. The reaction was carried out by microwave irradiation resulting 91 % yield. The obtained compound was then reacted with 2-methoxbenzaldehyde or 4-nitrobenzaldehyde to accomplish the target molecule, N'-(2-methoxybenzylidene)-4-hydroxybenzohydrazide and N'-(4-nitrobenzylidene)-4-hydroxybenzohydrazide in 55% and 72% yield respectively. Identification of N'-(2-methoxybenzylidene)-4-hydroxy benzo hydrazide and N'-(4-nitrobenzylidene)-4-hydroxybenzohidroksida was performed by FT-IR, MS,1H-NMR, and13C-NMR spectroscopy. In silico study was done with receptor pdb 1C14. The N'-(4-nitrobenzylidene)-4-hydroxybenzohydrazide exhibited antimicrobial activity against Escherichia coli (MIC=31.3 ppm), Bacillus subtilis (MIC=500 ppm). Antimicrobial activity of N'-(2-methoxybenzylidene)-4-hydroxybenzohydrazide against Bacillus subtilis (MIC=31.3 ppm) and MIC= 500 ppm against Escherichia coli.
Suzana,Isnaeni,Budiati, Tutuk
p. 16 - 20
(2017/03/13)

Synthesis, characterization and anti mycobacterial activity of novel hydrazones
The hydrazone Schiff base analogues namely benzoic acid (4-allyloxy-benzylidene)-hydrazide and its series were designed and synthesized. The structures of newly synthesized compounds were characterized by analytical methods and spectral analysis and subjected to antibacterial and docking studies. The synthesized molecules were subjected to molecular docking studies using enoyl-acyl-carrier protein reductase (NADH) from mycobacterium tuberculosis as the receptor. The docking results confirm the binding affinity of the synthesized compounds with the selected receptor. Preliminary in-vitro anti bacterial studies were carried out with Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria. Benzoic acid (4-allyloxy-benzylidene)-hydrazide was found to be most potent anti tuberculosis agent at 200 and 100μg per ml, the percentage of inhibition was 98.7% and 97.9%. The designed synthesized molecules were considered for evaluation for the molecular docking studies of their binding pattern with enoyl-acyl-carrier protein reductase from Mycobacterium tuberculosis. The antimycobacterial screening was performed against MTB H37Rv an isoniazid-resistant clinical isolate of MTB was used for the study.
Therese, S Kulandai,Geethamalika
p. 335 - 345
(2017/03/17)

Synthesis and biological evaluation of 1,2,4-triazole-3-thione and 1,3,4-oxadiazole-2-thione as antimycobacterial agents
Resistance among dormant mycobacteria leading to multidrug-resistant and extremely drug-resistant tuberculosis is one of the major threats. Hence, a series of 1,2,4-triazole-3-thione and 1,3,4-oxadiazole-2-thione derivatives (4a–5c) have been synthesized and screened for their antitubercular activity against Mycobacterium tuberculosis H37Ra (H37Ra). The triazolethiones 4b and 4v showed high antitubercular activity (both MIC and IC50) against the dormant H37Ra by in vitro and ex vivo. They were shown to have more specificity toward mycobacteria than other Gram-negative and Gram-positive pathogenic bacteria. The cytotoxicity was almost insignificant up to 100?μg/ml against THP-1, A549, and PANC-1 human cancer cell lines, and solubility was high in aqueous solution, indicating the potential of developing these compounds further as novel therapeutics against tuberculosis infection.
Sonawane, Amol D.,Rode, Navnath D.,Nawale, Laxman,Joshi, Rohini R.,Joshi, Ramesh A.,Likhite, Anjali P.,Sarkar, Dhiman
p. 200 - 209
(2017/07/13)