- Facile synthesis of new N -sulfonamidyl-4-thiazolidinone derivatives and their biological evaluation
-
The one-pot three-component syntheses of new N-sulfonamide-thiazolidin-4-one derivatives were carried out in excellent yield using [HDBU][HSO4] as an ionic liquid under solvent-free conditions. The newly synthesized compounds were screened against fungal strains and a number of compounds were seen to display excellent antifungal activity. In addition, the synthesized compounds were screened for their scavenging activity of the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical and showed very good antioxidant activity. Finally, theoretical predictions derived from molecular docking studies against the potential target sterol 14α-demethylase (CYP51) helped establish a link between the observed biological activity and the binding affinity, thereby providing insights into the specific bonding and non-bonding interactions governing the activity.
- Subhedar, Dnyaneshwar D.,Shaikh, Mubarak H.,Kalam Khan, Firoz A.,Sangshetti, Jaiprakash N.,Khedkar, Vijay M.,Shingate, Bapurao B.
-
-
Read Online
- Synthesis, Molecular Modeling, and Evaluation of Novel Sulfonylhydrazones as Acetylcholinesterase Inhibitors for Alzheimer's Disease
-
Alzheimer's disease (AD) is the most common type of dementia and related to the degeneration of hippocampal cholinergic neurons, which dramatically affects cognitive ability. Acetylcholinesterase (AChE) inhibitors are employed as drugs for AD therapy. Three series of sulfonylhydrazone compounds were designed, and their ability to inhibit AChE was evaluated. Fifteen compounds were synthesized and twelve of them had IC50 values of 0.64–51.09 μM. The preliminary structure–activity relationships indicated that the methylcatechol moiety and arylsulfonyl substituents generated better compounds than both the benzodioxole and alkylsulfonyl chains. Molecular dynamics studies of compound 6d showed that the interaction with the peripheral binding site of AChE was similar to donepezil, which may explain its low IC50 (0.64 μM). Furthermore, the drug-likeness of 6d suggests that the compound may have appropriate oral absorption and brain penetration. Compound 6d also presented antiradical activity and was not cytotoxic to LL24 cells, suggesting that this compound might be considered safe. Our findings indicate that arylsulfonylhydrazones may be a promising scaffold for the design of new drug candidates for the treatment of AD.
- Fernandes, Thais B.,Cunha, Micael R.,Sakata, Renata P.,Candido, Thalita M.,Baby, André R.,Tavares, Maurício T.,Barbosa, Euzébio G.,Almeida, Wanda P.,Parise-Filho, Roberto
-
-
Read Online
- Green synthesis of novel pyrazolo-fused benzophenazines using H3PW12O40 as efficient and recyclable catalyst under microwave irradiation
-
A high-yield, atom-efficient, and green protocol for the synthesis of novel pyrazolo-fused benzophenazines utilizing a multicomponent condensation reaction between 2-hydroxynaphthalene-1,4-dione, o-phenylenediamine, aromatic aldehydes, and 4-methylbenzenesulfonohydrazide in the presence of phosphotungstic acid (H3PW12O40) under microwave irradiation (MWI) in EtOH is reported. We provide a novel series of 1H-benzo[a]pyrazolo[3,4-c]phenazine derivatives interesting for biological screening tests. This protocol offers several advantages satisfying many principles of green chemistry, including atom economy, energy saving, clean reactions, inexpensive reagents, reusability of H3PW12O40, the absence of any tedious work-up or purification, and avoidance of hazardous or toxic reagents/catalysts/solvents.
- Mohebat, Razieh,Dehgan, Parisa,Yazdani-Elah-Abadi, Afshin
-
-
Read Online
- Synthesis and potential anticonvulsant activity of new aryl sulfonyl semicarbazide derivatives
-
In the present study on the development of new anticonvulsants, twelve new aryl sulfonyl semicarbazide derivatives were synthesized and tested for anticonvulsant activity using maximal electroshock (MES), subcutaneous pentylenetetrazole screens. Their neurotoxicity was determined by the rotorod test. The most active compound 5i showed the MES-induced seizures with ED50 value of 7.3?mg/kg and TD50 value of 402.3?mg/kg after intraperitoneally injection to mice, which provided compound 5i with a protective index (TD50/ED50) of 55.1 in the MES test.
- Nie, Yousong,Zhong, Min,Jiang, Zhiyuan,Sun, Jian,Gao, Yangguang,Ding, Fei,Li, Hang,Zhang, Yongmin,He, Xianran
-
-
Read Online
- Synthesis, biological activities and molecular docking simulation of hydrazone scaffolds of carvacrol, thymol and eugenol
-
In present work, we report the synthesis of 12 new hydrazones and sulfonyl hydrazones linkage containing carvacrol, thymol and eugenol derivatives by simple condensation reactions. Synthesized derivatives have been characterized by 1H NMR, 13C NMR, LC–MS, and X-ray single crystallography techniques, and these derivatives were screened for anticancer testing by using sulforhodamine B assay and anti-oxidant testing by using DPPH assay. Docking studies of all the derivatives against the active site of human heme oxygenase-1 indicated that interaction with the maximum site of the amino acid residue of human heme oxygenase-1 was crucial for anti-oxidant activity. The results show that all derivatives possess interesting biological activities.
- Rajput, Jamatsing D.,Bagul, Suresh D.,Bendre, Ratnamala S.
-
-
Read Online
- Synthesis, molecular structure, photoluminescence, multiple interaction, chemical reactivity and first hyperpolarizability analysis of ethyl 2-cyano-3-{5-(4-methylbenzenesulfonyl)-hydrazonomethyl]-1H-pyrrol-2-yl} -acrylate: Experimental and quantum chemical approaches
-
A detailed spectroscopic, molecular structure, photoluminescence, multiple interaction, chemical reactivity and first hyperpolarizability analysis of a newly synthesized ethyl 2-cyano-3-{5-[(4-methylbenzenesulfonyl)-hydrazonomethyl] -1H-pyrrol-2-yl}-acrylate (ECMHPA) has been carried out. TD-DFT is used to find various electronic excitations and their nature within molecule. The emission spectra show photoluminescence behavior of title molecule in yellow region. The red shift in both the proton donor (pyrrole NH) and proton acceptor (SO) group designates the presence of intermolecular hydrogen bonding N1H2a?O49 and N46H47a?O4. The binding energy of dimer formation has been calculated to be 12.12 kcal/mol after basis set superposition error (BSSE) correction. The global electrophilicity index (ω = 5.44 eV) shows that ECMHPA is a strong electrophile. First hyperpolarizability (β0) of ECMHPA has been computed to evaluate non-linear optical (NLO) response of the investigated molecule.
- Singh,Rawat, Poonam,Kumar, Amit
-
-
Read Online
- Copper-Catalyzed Radical Cascade Cyclization to Access 3-Sulfonated Indenones with the AIE Phenomenon
-
An efficient copper-catalyzed radical cascade cyclization strategy was developed, by which a wide variety of 3-sulfonyl substituted indenones were prepared in one pot via reaction of 2-alkynylbenzonitriles with sulfonyl hydrazides in the presence of TBHP and CuI under mild reaction conditions. Much more importantly, the 3-sulfonyl indenones, synthesized through our newly developed copper-catalyzed radical cascade cyclization strategy, were found to own typical aggregation-induced emission (AIE) properties, showing orange to red emission with large Stokes shift (more than 135 nm). In addition, such newly found AIEgens could be successfully used in live cell imaging, exhibiting excellent biocompatibility and application potential.
- Sun, Kai,Chen, Xiao-Lan,Li, Shi-Jun,Wei, Dong-Hui,Liu, Xiao-Ceng,Zhang, Yin-Li,Liu, Yan,Fan, Lu-Lu,Qu, Ling-Bo,Yu, Bing,Li, Kai,Sun, Yuan-Qiang,Zhao, Yu-Fen
-
-
Read Online
- Synthesis, characterization and biological evaluation of some novel sulfonylthiosemicarbazides
-
A series of thiosemicarbazides were synthesized and structurally characterized by spectroscopic techniques (NMR, FT-IR) besides elemental analysis. These compounds were evaluated for their cytotoxicity against human breast cancer cell line MCF7 and prostate cancer cell line PC3 and nonmalignant fibroblast L929 cell line by MTT assay. Among the compounds, N-[2-(4-chlorophenyl)ethyl]-2-[(4-methylphenyl)sulfonyl]hydrazinecarbothioamide (3d) and 2-[(4-methylphenyl)sulfonyl]-N-[4-(trifluoromethoxy)phenyl]hydrazinecarbothioamide (3f) were found to display significant cytotoxicity with IC50 of 13.87 μM (against PC3 cell line) and 1.47 μM (against MCF7 cell line), respectively. These compounds were non-cytotoxic to normal cell line with IC50>100 μM. Western blotting studies demonstrated that compound 3f induced apoptosis and caused cell death in the MCF7 and PC3 cell lines via an increase in Bax protein expression and a slight decrease in Bcl-2 protein expression. The gene expression ratio Bax/Bcl-2 showed the induction of mitochondrial apoptosis in cancer cell lines. All of synthesized compounds have also been tested for antioxidant activity and all compounds achieved strong inhibition of the DPPH radical. These findings showed that compound 3f, displays potential to be further explored in the development of new anticancer agents.
- ?enkarde?, Sevil,Han, ?hsan,Han?er, Hakan,Abbak, Mürüvvet,?evik, ?zge,Güniz Kü?ükgüzel
-
-
Read Online
- Design, synthesis, biological evaluation and in silico studies of certain aryl sulfonyl hydrazones conjugated with 1,3-diaryl pyrazoles as potent metallo-β-lactamase inhibitors
-
Based on a structure-guided approach, aryl sulfonyl hydrazones conjugated with 1,3-diaryl pyrazoles were designed to target metallo-β-lactamases (MBLs), using Klebsiella pneumoniae NDM-1 as a model. The in vitro MBLs inhibition showed remarkable inhibition constant for most of the designed compounds at a low micromolar range (1.5–16.4 μM) against NDM-1, IMP-1 and AIM-1 MBLs. Furthermore, all compounds showed promising antibacterial activity against (K+, K1-K9) resistant clinical isolates of K. pneumoniae and were able to re-sensitize resistant K. pneumoniae (K5) strain towards meropenem and cefalexin. Besides, in vivo toxicity testing exhibited that the most active compound was non-toxic and well tolerated by the experimental animals orally up to 350 mg/kg and up to 125 mg/kg parenterally. The docking experiments on NDM-1 and IMP-1 rationalized the observed in vitro MBLs inhibition activity. Generally, this work presents a fruitful matrix to extend the chemical space for MBLs inhibition. This aids in tackling drug-resistance issues in antibacterial treatment.
- Shaaban, Marwa M.,Ragab, Hanan M.,Akaji, Kenichi,McGeary, Ross P.,Bekhit, Alaa-Eldin A.,Hussein, Waleed M.,Kurz, Julia L.,Elwakil, Bassma H.,Bekhit, Salma A.,Ibrahim, Tamer M.,Mahran, Mona A.,Bekhit, Adnan A.
-
-
Read Online
- A highly selective and sensitive dual-channel chemosensor for cyanide based on sulfahydrazone derivative
-
A colorimetric and fluorescent cyanide probe bearing naphthol and sulfahydrazone groups has been designed and synthesized. This structurally simple probe displays a rapid response and high selectivity for cyanide in DMSO/EtOH (v/v = 2:8) solution. The addition of CN? to the sensor p-toluenesulfonyl-2-hydroxy-1-naphthylhydrazone (L3) induced a remarkable color change from pale-yellow to yellow, and green fluorescence changed to yellow. The 1H NMR titration and DFT calculations suggested that the selective sensing process is based on a nucleophilic addition reaction of cyanide to imine. Test strips based on sensor L3 were fabricated, which could act as a convenient and efficient test kit to detect CN? for “in-the-field” measurements.
- Leng, Yan-Li,Zhang, Jian-Hui,Li, Qiao,Zhang, You-Ming,Lin, Qi,Yao, Hong,Wei, Tai-Bao
-
-
Read Online
- Development of pyrazole and spiropyrazoline analogs as multifunctional agents for treatment of Alzheimer's disease
-
Cholinergic hypothesis of Alzheimer's disease has been advocated as an essential tool in the last couple of decades for the drug development. Here in, we report de novo fragment growing strategy for the design of novel 3,5-diarylpyrazoles and hit optimization of spiropyrazoline derivatives as acetyl cholinesterase inhibitors. Both type of scaffolds numbering forty compounds were synthesized and evaluated for their potencies against AChE, BuChE and PAMPA. Introduction of lipophilic cyclohexane ring in 3,5-diarylpyrazole analogs led to spiropyrazoline derivatives, which facilitated and improved the potencies. Compound 44 (AChE = 1.937 ± 0.066 μM; BuChE = 1.166 ± 0.088 μM; hAChE = 1.758 ± 0.095 μM; Pe = 9.491 ± 0.34 × 10?6 cm s1) showed positive results, which on further optimization led to the development of compound 67 (AChE = 0.464 ± 0.166 μM; BuChE = 0.754 ± 0.121 μM; hAChE = 0.472 ± 0.042 μM; Pe = 13.92 ± 0.022 × 10?6 cm s1). Compounds 44 and 67 produced significant displacement of propidium iodide from the peripheral anionic site (PAS) of AChE. They were found to be safer to MC65 cells and decreased metal induced Aβ1-42 aggregation. Further, in-vivo behavioral studies, on scopolamine induced amnesia model, the compounds resulted in better percentage spontaneous alternation scores and were safe, had no influence on locomotion in tested animal groups at dose of 3 mg/kg. Early pharmacokinetic assessment of optimized hit molecules was supportive for further drug development.
- Gutti, Gopichand,Kumar, Devendra,Paliwal, Pankaj,Ganeshpurkar, Ankit,Lahre, Khemraj,Kumar, Ashok,Krishnamurthy, Sairam,Singh, Sushil Kumar
-
-
Read Online
- Biological evaluation of p-toluene sulphonylhydrazone as carbonic anhydrase IX inhibitors: An approach to fight hypoxia-induced tumors
-
To find potential inhibitors of human carbonic anhydrase IX (CAIX), we have successfully deigned, synthesized and characterized three p-toluene sulphonylhydrazone derivatives (1–3). Molecular docking studies provided the structural basis of CAIX inhibition and a deeper insight into the protein-ligand interactions. p-Toluene sulphonylhydrazone derivatives show a well organized conformational compatibility with the active site of CAIX. The protein-ligand complex was stabilized by several non-covalent interactions offered by residues present in the active site cavity. The actual binding affinity of synthesized compounds with CAIX was experimentally measured by fluorescence and isothermal titration calorimetry (ITC). Results of both fluorescence binding and ITC measurements show the binding affinity of p-Toluene sulphonylhydrazone derivatives to the CAIX in the μM range. CAIX enzyme inhibition assay showed the IC50 values in nM range. Though all the three compounds (1–3) showed a good binding with CAIX, compound 2 showed the best inhibition of CAIX activity. These compounds were non-toxic on normal cell lines (HEK-293) and significantly inhibit the proliferation of hypoxic cancer cells. All compounds induce apoptosis in the hypoxic cancer cells. These compounds may be further exploited as promising therapeutic agents to control the hypoxia-induced tumors.
- Queen, Aarfa,Khan, Parvez,Idrees, Danish,Azam, Amir,Hassan, Md. Imtaiyaz
-
-
Read Online
- Synthesis, molecular structure, quantum mechanical studies and urease inhibition assay of two new isatin derived sulfonylhydrazides
-
Two new isatin derivatives (E)-N′-(1-allyl-2-oxoindolin-3-ylidene)-4-methylbenzenesulfono-hydrazide (5) and (E)-N′-(1-allyl-2-oxoindolin-3-ylidene)-4-chlorobenzenesulfono-hydrazide (6) were synthesized in good yields by adopting two component synthetic methodology. The structure elucidation was accomplished with the help of UV–vis., FT-IR and NMR (1H and 13C) spectroscopic techniques. Suitable crystals were grown by slow evaporation method and structures were confirmed unequivocally with the help of single crystal X-ray diffraction analysis. Both isatin derivatives 5 and 6 exist in triclinic crystal packing having space group P-1. Crystal structures of both compounds showed that the geometries are stabilized by several intermolecular hydrogen bonds. Quantum mechanical calculations performed at density functional theory (DFT) level confirmed the experimental spectroscopic (UV–vis., FT-IR and 1H NMR) as well as X-ray diffraction results. Kinetic stability, reactivity, electrophilicity and nucleophilic behavior of both the derivatives was elaborated using frontier molecular orbitals (FMOs) and molecular electrostatic potential (MEP) analyses. Enzyme inhibition potential of both compounds was tested in vitro against Bacillus pasteurii urease and both compounds retarded the enzymatic activity with IC50 values of 39.46 ± 0.12 μM and 148.35 ± 0.16 μM respectively.
- Arshad, Muhammad,Jadoon, Mehwish,Iqbal, Zafar,Fatima, Mehwish,Ali, Muhammad,Ayub, Khurshid,Qureshi, Ashfaq Mahmood,Ashraf, Muhammad,Arshad, Muhammad Nadeem,Asiri, Abdullah M.,Waseem, Amir,Mahmood, Tariq
-
-
Read Online
- Copper(I)/Bpy-Catalyzed C-2-H Benzylation of Quinazolin-4(3H)-ones with N-Tosylhydrazones
-
A general and efficient copper-catalyzed C–H benzylation reaction of quinazolin-4(3H)-ones with N-tosylhydrazones is reported. The formation of new C(sp3)–C(sp2) bonds through cross-coupling occurs at the electron-poor C-2 position of quinazolin-4(3H)-one and represents an exceedingly practical method to afford 2-benzylated quinazolin-4(3H)-ones in moderate to good yields under mild reaction conditions. A possible reaction mechanism for this transformation was proposed. This catalytic transformation has the potential to be an important synthetic application for the late-stage functionalization of advanced synthetic intermediates.
- Li, Fei,Gu, Xiao-Juan,Zeng, Chang-E.,Li, Xia,Liu, Bo,Huang, Guo-Li
-
-
Read Online
- Electrochemical characterization of para- and meta-nitro substituents in aqueous media of new antichagasic pharmaceutical leaders
-
The electrochemical reduction mechanism of two isomers of position drug leaders against Chagas disease, p-nitrosulfonylhydrazine derivative (p-NSF), and m-nitrosulfonylhydrazine derivative (m-NSF), was investigated in aqueous media and in the absence of oxygen using voltammetric techniques. The main reduction process was attributed to the reduction of the nitro group (Epc (p-NSF) = ?0.58 V and Epc (m-NSF) = ?0.62 V), generating nitroso derivative in intermediate and higher values of pH and hydroxylamine in lower values of pH. Another reduction process in a less negative potential value was only observed for p-NSF and attributed to the generation of the nitro radical anion. The difference in the reduction potentials between both compounds and the presence of another reduction process for p-NSF was associated with the position of the nitro group, due to the distinct stabilization of the reduction intermediates by the aromatic ring. A catalytic response for the reduction process of the nitro anion radical was observed for p-NSF in the presence of oxygen, given that its magnitude of current increased when increasing the oxygen availability. Also, for m-NSF, this reduction process could be detected, even though it was not observed in the voltammograms in the absence of oxygen. This further confirmed the generation of the nitro radical anion, since it reacts with molecular oxygen and regenerates the initial nitro compound. The interaction with cysteine was also evaluated, which favored the reduction process towards the generation of the nitroso derivative due to adduct formation, destabilizing the reduction process regarding the nitro radical anion. Therefore, electrochemical experiments can evaluate how different isomers of position and other coupled functional groups affect the reduction of the nitro group and, consequently aid in the design of new classes of antichagasic pharmaceuticals, with improved stability of reactive intermediates that are often correlated with the degree of injury towards the parasite.
- Sanz, Caroline G.,Dias, Kevin A.,Bacil, Raphael P.,Serafim, Ricardo A.M.,Andrade, Leandro H.,Ferreira, Elizabeth I.,Serrano, Silvia H.P.
-
-
- Design of arylsulfonylhydrazones as potential fabh inhibitors: Synthesis, antimicrobial evaluation and molecular docking
-
Background: Antimicrobial resistance is a persistent problem regarding infection treatment and calls for developing new antimicrobial agents. Inhibition of bacterial β-ketoacyl acyl carrier protein synthase III (FabH), which catalyzes the condensation reaction between a CoA-attached acetyl group and an ACP-attached malonyl group in bacteria is an interesting strategy to find new antibacterial agents. Objective: The aim of this work was to design and synthesize arylsulfonylhydrazones potentially FabH inhibitors and evaluate their antimicrobial activity. Methods: MIC50 values of sulfonylhydrazones against E. coli and S. aureus were determined. An-tioxidant activity was evaluated by DPPH (1-1’-diphenyl-2-picrylhydrazyl) assay and cytotoxicity against LL24 lung fibroblast cells was verified by MTT method. Principal component analysis (PCA) was performed in order to suggest a structure-activity relationship. Molecular docking allowed to propose sulfonylhydrazones interactions with FabH. Results: The most active compound showed activity against S. aureus and E. coli, with MIC50 = 0.21 and 0.44 μM, respectively. PCA studies correlated better activity to lipophilicity and molecular docking indicated that sulfonylhydrazone moiety is important to hydrogen-bond with FabH while methylcatechol ring performs π-π stacking interaction. The DPPH assay revealed that some sulfonylhydrazones derived from the methylcatechol series had antioxidant activity. None of the evaluated compounds was cytotoxic to human lung fibroblast cells, suggesting that the compounds might be considered safe at the tested concentration. Conclusion: Arylsufonylhydrazones is a promising scaffold to be explored for the design of new antimicrobial agents.
- Fernandes, Thais Batista,Segretti, Natanael Dante,Louren?o, Felipe Rebello,Candido, Thalita Marcílio,Baby, André Rolim,Barbosa, Euzébio Guimar?es,Parise-Filho, Roberto
-
p. 474 - 484
(2021/03/26)
-
- Palladium-Catalyzed Direct C-H Arylation of 3-Butenoic Acid Derivatives
-
We report herein a direct method to synthesize 4-aryl-3-butenoic acid through a carboxylic-acid-directed oxidative Heck reaction. The various 4-aryl-3-butenoic acids are easily prepared in moderate to good yields. In view of the promising bioactivity of 4-phenyl-3-butenoic acid previously reported, its derivatives reported here may be bioactive.
- Yang, Shan,Liu, Lingling,Zhou, Zheng,Huang, Zhibin,Zhao, Yingsheng
-
supporting information
p. 296 - 299
(2021/01/13)
-
- Electrochemical heterodifunctionalization of α-CF3alkenes to access α-trifluoromethyl-β-sulfonyl tertiary alcohols
-
An unprecedented electrochemical heterodifunctionalization of α-CF3alkenes with benzenesulfonyl hydrazides was accomplished in this work, wherein a β-sulfonyl and a α-hydroxyl group were simultaneously incorporated across the olefinic double bond in a single operation. Consequently, a series of potentially medicinally valuable and densely functionalized α-trifluoromethyl-β-sulfonyl tertiary alcohols were assembled under mild conditions. Electrochemically-driven oxidative 1,2-difunctionlization of electron-deficient alkenes well obviates the need for oxidizing reagents, thus rendering this protocol more eco-friendly.
- Chen, Kai,Duan, Xin-Yu,Gao, Jie,Guan, Jian-Ping,Liu, Fang,Xiang, Hao-Yue,Xiao, Jun-An,Yang, Hua,Ye, Zhi-Peng
-
supporting information
p. 8969 - 8972
(2021/09/10)
-
- Electrochemical fluorosulfonylation of styrenes
-
An environmentally friendly and efficient electrochemical fluorosulfonylation of styrenes has been developed. With the use of sulfonylhydrazides and triethylamine trihydrofluoride, a diverse array of β-fluorosulfones could be readily obtained. This reaction features mild conditions and a broad substrate scope, which could also be conveniently extended to a gram-scale preparation.
- Jiang, Yi-Min,Wu, Shao-Fen,Yan, Hong,Ye, Ke-Yin,Yu, Yi,Yuan, Yaofeng
-
supporting information
p. 11481 - 11484
(2021/11/16)
-
- Synthesis and hyperglycemic, biochemical and histopathological evaluation of novel sulfonylbiguanide and sulfonylurea derivatives as potent anti-diabetic agents
-
New sulfonylbiguanide hydrochloride salts and sulfonylurea derivatives containing two sulfonyl groups were synthesized through the reaction of arylsulfonohydrazides with cyanoguanidine and p-tolylsulfonylisocyanate, respectively. Oral treatment of hyperglycemic rats with the synthesized sulfonylbiguanide derivatives 2 and sulfonylurea derivatives 3 revealed that sulfonylurea derivatives 3a and 3c possessed significant decrease of the elevated glucose in compression with the anti-diabetic standard drugs. Effects of the synthesized sulfonylurea derivatives 3a and 3c on the diabetic properties towards α-amylase, liver function enzyme levels (AST, ALT, ALP, TB and γ-GT), kidney functions (urea and creatinine), lipids profiles (TG, TL, TC and HDL-C) were studied. Also, the effect of sulfonylurea derivatives 3a and 3c as antioxidants (reduced glutathione and lipid peroxide) was evaluated. Histopathological examination of hepatic and pancreatic tissues was investigated. The obtained results suggested that the most potent sulfonylurea derivatives 3a and 3c might be possible used as novel diabetic inhibitor agents.
- Basyouni, Wahid M.,Abbas, Samir Y.,El-Bayouki, Khairy A.M.,Younis, Eman A.,Ali, Sanaa A.,Aly, Hanan F.
-
-
- Dual Roles of Rongalite: Reductive Coupling Reaction to Construct Thiosulfonates Using Sulfonyl Hydrazides
-
A tunable and practical transformation of structurally diverse sulfonyl hydrazides into thiosulfonates in the presence of Rongalite (NaHSO 2·CH 2O) was developed. Transition-metal-free conditions, operational simplicity, and readily available reagents are the striking features of this protocol. It is the first example for the synthesis of thiosulfonates using sulfonyl hydrazides with the assistance of reductant. Additionally, the mechanistic studies revealed that this transformation probably undergoes via a reducing-coupling pathway.
- Zhang, Guofu,Fan, Qiankun,Zhao, Yiyong,Wang, Huimin,Ding, Chengrong
-
supporting information
p. 81 - 85
(2020/11/03)
-
- Iodine-Mediated Coupling of Cyclic Amines with Sulfonyl Hydrazides: an Efficient Synthesis of Vinyl Sulfone Derivatives
-
An efficient iodine-mediated coupling of cyclic amines with sulfonyl hydrazides is reported. This transformation opens a new route to the synthesis of vinyl sulfones derivatives, which is a common structural motif in natural products and pharmaceuticals. Tentative mechanistic studies suggest that this reaction is likely to involve a radical process.
- Rong, Xiaona,Guo, Jingwen,Hu, Zheqi,Huang, Lehao,Gu, Yugui,Cai, Yuepiao,Liang, Guang,Xia, Qinqin
-
supporting information
p. 701 - 708
(2020/12/30)
-
- NaHSO3-Mediated Direct Synthesis of Sulfinic Esters from Sulfonyl Hydrazides under Transition-Metal-Free Conditions
-
We have developed a protocol for the NaHSO3-promoted esterification of sulfonyl hydrazides with alcohols for the synthesis of sulfinic esters. Various sulfonyl hydrazides could be converted to the corresponding sulfinic esters in good to high yields. The merits of this protocol include mild transition-metal-free reaction conditions, an inexpensive and available reagent, and operational simplicity. Controlled experiments reveal that this transformation probably undergoes via a radical pathway. (Figure presented.).
- Zhang, Guofu,Fan, Qiankun,Wang, Huimin,Zhao, Yiyong,Ding, Chengrong
-
supporting information
p. 833 - 837
(2020/12/07)
-
- Palladium-Catalyzed Asymmetric Hydrosulfonylation of 1,3-Dienes with Sulfonyl Hydrazides
-
A highly enantio- and regioselective hydrosulfonylation of 1,3-dienes with sulfonyl hydrazides has been realized by using a palladium catalyst containing a monodentate chiral spiro phosphoramidite ligand. The reaction provided an efficient approach to synthetically useful chiral allylic sulfones. Mechanistic studies suggest that the reaction proceeds through the formation of an allyl hydrazine intermediate and subsequent rearrangement to the chiral allylic sulfone product. The transformation of the allyl hydrazine intermediate to the product is the enantioselectivity-determining step.
- Li, Ming-Ming,Cheng, Lei,Xiao, Li-Jun,Xie, Jian-Hua,Zhou, Qi-Lin
-
supporting information
p. 2948 - 2951
(2020/12/15)
-
- One-pot synthesis of sulfonylhydrazones from sulfonyl chloride, hydrazine hydrate and vinyl azide in water
-
A facile and eco-friendly protocol for the synthesis of sulfonylhydrazones from sulfonyl chlorides, hydrazine hydrate and vinyl azides was developed. The unique advantage of this approach is that desired products can be obtained efficiently in water, which meets the requirements of green chemistry and provides good perspectives for the sustainable production of new drug candidate. Also, this reaction proceeded in moderate to good yields with a wide tolerance of functional groups.
- Luo, Mengqiang,Wang, Hai,Ren, Xiaorong,Lu, Ruijuan,Qi, Chenze,Zhang, Yaohong,Shen, Runpu
-
p. 2713 - 2722
(2021/03/19)
-
- Synthesis of symmetrical / unsymmetrical thiosulfonates through the disproportionate coupling reaction of sulfonyl hydrazide mediated by phosphomolybdic acid
-
Phosphomolybdic acid (H3PMo12O40) is reported as a green low-cost catalyst for the synthesis of symmetrical / unsymmetrical thiosulfonates via the disproportionate coupling reaction of sulfonyl hydrazide. The attributes of this reported catalytic system include low catalyst loadings (1 mol%), efficient turnover, and high yields (up to 94%). Additionally, this reaction mechanism involves the formation of a thiyl radical and sulfonyl radical via sulfinyl radical disproportionation.
- Lv, Mengting,Liu, Yufeng,Li, Ke,Yang, Guoping
-
supporting information
(2021/01/21)
-
- Inhibitory Evaluation and Molecular Docking Analysis of Benzenesulfonamides on Carbonic Anhydrase II
-
Abstract: Sulfonamides is an important class of compounds, which can be used as carbonic anhydrase inhibitors. Nine different benzenesulfonamide compounds were synthesized, and their inhibitory effects on carbonic anhydrase II were studied by esterase method and molecular docking. The results showed that compounds (IId)–(IIg) with nitro and acetamide groups on the benzene ring exhibited excellent carbonic anhydrase II inhibitory activities. Molecular docking showed that compared with the control inhibitor acetazolamide, the compounds (IId)–(IIg) docked at the carbonic anhydrase II active site and showed higher binding energy and stronger binding ability. The physical and chemical properties of all compounds were studied by Molinspiration, which showed outstanding drug-like properties and ADME properties. Cytotoxicity assay results showed that compounds (IIe) and (IIf) were almost non-toxic to HepG2 and RAW264.7 cells. In conclusion, the compounds (IIe) and (IIf) have a certain application prospect as new inhibitors of carbonic anhydrase II.
- Zhang,Wei,Liu,Wu,Xuan
-
p. 261 - 269
(2021/03/23)
-
- Photomechanical response of sulfonylhydrazone molecular crystals
-
Sulfonylhydrazones are a novel hydrazone-based organic molecular photoswitch. The four derivatives with unsubstituted ando-,m- andp-nitro substituted sulfonylhydrazone (SH-1,SH-2,SH-3, andSH-4, respectively) derived fromp-toluenesulfonyl hydrazide and corresponding benzaldehydes were examined with respect to their solution state photoswitching and photomechanical response in the crystalline state. All the compounds displayed UV-inducedE→Zisomerization in the solution state, whereas the back conversion was slow. Single crystals ofSH-3displayed rapid and large photomechanical bending, whereasSH-1andSH-4crystals underwent slow bending to a comparatively lesser extent. On the contrary,SH-2crystals did not show any photomechanical effects. The photomechanical deflection of the crystal tip ofSH-1increased linearly; forSH-3, the deflection increased in a sub-linear manner for few seconds, after which it started to revert towards the light source. ForSH-4crystals, the photo-induced tip deflection initially increased in a sub-linear fashion, after which no motion was observed even after continuous exposure to UV light irradiation. The photomechanical behavior of the crystals was also inspected with the aid of velocity-time and acceleration-time plots that unravelled the instantaneous photomechanical motion at various time intervals.
- Allu, Suryanarayana,Gunnam, Anilkumar,Gupta, Poonam,Hazarika, Pragyan J.,Nangia, Ashwini K.,Nath, Naba K.
-
p. 4910 - 4916
(2021/07/25)
-
- Small molecule-mediated induction of endoplasmic reticulum stress in cancer cells
-
The endoplasmic reticulum (ER) is one of the crucial sub-cellular organelles controlling myriads of functions including protein biosynthesis, folding, misfolding and unfolding. As a result, dysregulation of these pathways in the ER is implicated in cancer development and progression. Subsequently, targeting the ER in cancer cells emerged as an interesting unorthodox strategy in next-generation anticancer therapy. However, development of small molecules to selectively target the ER for cancer therapy remained elusive and unexplored. To address this, herein, we have developed a novel small molecule library of sulfonylhydrazide-hydrazones through a short and concise chemical synthetic strategy. We identified a fluorescent small molecule that localized into the endoplasmic reticulum (ER) of HeLa cells, induced ER stress followed by triggering autophagy which was subsequently inhibited by chloroquine (autophagy inhibitor) to initiate apoptosis. This small molecule showed remarkable cancer cell killing efficacy in different cancer cells as mono and combination therapy with chloroquine, thus opening a new direction to illuminate ER-biology towards the development of novel anticancer therapeutics.
- Basu, Sudipta,Biswas, Ankur,Lahiri, Mayurika,Pandey, Shalini,Sharma, Virender Kumar
-
supporting information
p. 1604 - 1611
(2021/10/23)
-
- Acridine Orange Hemi(Zinc Chloride) Salt as a Lewis Acid-Photoredox Hybrid Catalyst for the Generation of α-Carbonyl Radicals
-
A readily accessible organic-inorganic hybrid catalyst is reported for the reductive fragmentation of α-halocarbonyl compounds. The robust hybrid catalyst is a self-stabilizing combination of ZnCl2 Lewis acid and acridine orange as the photoactive organic dye. Mechanistic specifics of this hybrid catalyst have been studied in detail using both photophysical and electrochemical experiments. A systematic study enabled the discovery of the appropriate Lewis acid for the effective LUMO stabilization of α-halocarbonyl compounds and thereby lowering of reduction potential within the range of a standard organic dye. This strategy resolves the issues like dehalogenative hydrogenation or homo-coupling of alkyl radicals by guiding the photoredox cycle through an oxidative quenching pathway. The cooperativity between the photoactive organic dye and the Lewis acid counterparts empowers functionalization with a wide range of coupling partners through efficient and controlled generation of alkyl radicals and serves as an appropriate alternative to the expensive late transition metal-based photocatalysts. To demonstrate the application potential of this cooperative catalytic system, four different synthetic transformations of α-carbonyl bromides were explored with broad substrate scopes.
- Das, Sanju,De Sarkar, Suman,Mandal, Tanumoy
-
supporting information
(2021/12/10)
-
- Electrochemical Annulation-Iodosulfonylation of 1,5-Enyne-containing para-Quinone Methides (p-QMs) to Access (E)-Spiroindenes
-
A new electrochemical three-component annulation-iodosulfonylation of 1,5-enyne-containing para-quinone methides (p-QMs) has been established by using available arylsulfonyl hydrazides and potassium iodide under environmentally benign conditions. The electrosynthesis offers sustainable and efficient access to construct spirocyclohexadienone-containing (E)-indenes without any additional catalyst or oxidant through a sulfonyl-radical-triggered 1,6-addition and an I+-mediated ipso-cyclization cascade. Notably, potassium iodide plays the triple role of an electrolyte, a redox catalyst, as well as an iodination reagent.
- Zuo, Hang-Dong,Zuo, Hang-Dong,Hao, Wen-Juan,Zhu, Chi-Fan,Zhu, Chi-Fan,Guo, Cheng,Tu, Shu-Jiang,Jiang, Bo
-
supporting information
p. 4471 - 4477
(2020/06/04)
-
- Synthesis, molecular docking and evaluation of novel sulfonyl hydrazones as anticancer agents and COX-2 inhibitors
-
Abstract: In trying to develop new anticancer agents, a series of sulfonylhydrazones were synthesized. All synthesized compounds were checked for identity and purity using elemental analysis, TLC and HPLC and were characterized by their melting points, FT-IR and NMR spectral data. All synthesized compounds were evaluated for their cytotoxic activity against prostate cancer (PC3), breast cancer (MCF-7) and L929 mouse fibroblast cell lines. Among them, N′-[(2-chloro-3-methoxyphenyl)methylidene]-4-methylbenzenesulfonohydrazide (3k) showed the most potent anticancer activity against both cancer cells with good selectivity (IC50 = 1.38?μM on PC3 with SI = 432.30 and IC50 = 46.09?μM on MCF-7 with SI = 12.94). Further investigation confirmed that 3k displayed morphological alterations in PC3 and MCF-7 cells and promoted apoptosis through down-regulation of the Bcl-2 and upregulation of Bax expression. Additionally, compound 3k was identified as the most potent COX-2 inhibitor (91% inhibition) beside lower COX-1 inhibition. Molecular docking of the tested compounds represented important binding modes which may be responsible for their anticancer activity via inhibition of the COX-2 enzyme. Overall, the lead compound 3k deserves further development as a potential anticancer agent. Graphic abstract: Sulfonylhydrazones was synthesized and N′-[(2-chloro-3-methoxyphenyl)methylidene]-4-methylbenzenesulfonohydrazide (3k) was identified as the most potent anticancer agent and COX-2inhibitor. In addition, this compound docked inside the active site of COX-2 succesfully. [Figure not available: see fulltext.].
- ?enkarde?, Sevil,Han, M. ?hsan,Kulaba?, Necla,Abbak, Mürüvvet,?evik, ?zge,Kü?ükgüzel, ?lkay,Kü?ükgüzel, ?. Güniz
-
p. 673 - 689
(2019/07/19)
-
- Synthesis, biological activities, and 3D-QSAR studies of (R)-2-phenyl-4,5-dihydrothiazole-4-carboxamide derivatives containing a sulfonohydrazide moiety
-
To discover a novel lead structure for antiphytopathogenic fungus agent, a series of (R)-2-phenyl-4,5-dihydrothiazole-4-carboxamide derivatives containing a sulfonohydrazide moiety were designed and synthesized. They were determined by melting points, 1H NMR, 13C NMR, and elemental analysis (EA). The biological activity results revealed that these title compounds possessed antifungal and insecticidal activities. Some title compounds against Alternaria solani, Physalospora piricola, Cercospora arachidicola, Phytophthora capsici, Fusarium graminearum, and Sclerotinia sclerotiorum displayed moderate to good antifungal activities at 50 mg/L, especially, compounds 6b and 6p displayed good and broad-spectrum antifungal activities. The structure activity relationships were discussed. A 3D-QSAR model was established based on the antifungal activity against Phytophthora capsici, indicating that electrostatic and hydrophobic fields were the two most significant factors for antifungal activity. Hence, structure optimization based on the CoMSIA model was performed to find compound 6p with excellent activity against Phytophthora capsici, and the EC50 values of compound 6p were comparable to those of chlorothalonil. Furthermore, the insecticidal activity of compound 6p against Culex pipiens larvae at 1 mg/L was considerable to that of chlorantraniliprole. Therefore, compound 6p can be used as a novel lead structure for antiphytopathogenic fungus and insecticidal agent development.
- Li, Fengyun,Li, Yuxin,Li, Zhengming,Liu, Jingbo,Wang, Yuanhong,Zhang, Haoxuan
-
-
- Synthesis, in vitro α-amylase inhibitory, and radicals (DPPH & ABTS) scavenging potentials of new N-sulfonohydrazide substituted indazoles
-
Over-expression of α-amylase enzyme causes hyperglycemia which lead to many physiological complications including oxidative stress, one of the most commonly associated problem with diabetes mellitus. Marketed α-amylase inhibitors such as acarbose, voglibose, and miglitol used to treat type-II diabetes mellitus, but also linked to several harmful effects. Therefore, it is essential to explore new and nontoxic antidiabetic agents with additional antioxidant properties. In this connection, a series of new N-sulfonohydrazide substituted indazoles 1–19 were synthesized by multistep reaction scheme and assessed for in vitro α-amylase inhibitory and radical (DPPH and ABTS) scavenging properties. All compounds were fully characterized by different spectroscopic techniques including 1H, 13C NMR, EI-MS, HREI-MS, ESI-MS, and HRESI-MS. Compounds showed promising α-amylase inhibitory activities (IC50 = 1.23 ± 0.06–4.5 ± 0.03 μM) as compared to the standard acarbose (IC50 1.20 ± 0.09 μM). In addition to that all derivatives were found good to moderate scavengers of DPPH (IC50 2.01 ± 0.13–5.3 ± 0.11) and ABTS (IC50 = 2.34 ± 0.07–5.5 ± 0.07 μM) radicals, in comparison with standard ascorbic acid having scavenging activities with IC50 = 1.99 ± 0.09 μM, and IC50 2.03 ± 0.11 μM for DPPH and ABTS radicals. In silico molecular docking study was conducted to rationalize the binding interaction of α-amylase enzyme with ligands. Compounds were observed as mixed type inhibitors in enzyme kinetic characterization.
- Rafique, Rafaila,Khan, Khalid Mohammed,Arshia,Chigurupati, Sridevi,Wadood, Abdul,Rehman, Ashfaq Ur,Salar, Uzma,Venugopal, Vijayan,Shamim, Shahbaz,Taha, Muhammad,Perveen, Shahnaz
-
-
- Designing heterocyclic chalcones, benzoyl/sulfonyl hydrazones: An insight into their biological activities and molecular docking study
-
The aim of this study is to investigate the antioxidant, anticholinesterase and the antiproliferative activities of some chalcones, benzoyl and sulfonyl hydrazones. The antioxidant activity was studied by way of four complimentary assays and the anticholinesterase activity was studied using the Ellman method. The antiproliferative activity of the compounds was determined using a BrdU cell proliferation ELISA assay. Compound 32 (IC50: 15.58 ± 0.01 μg/mL) against the brain (C6) and 29 (IC50: 5.02 ± 0.05 μg/mL) against cervical (HeLa) cancer cell lines exhibited higher antiproliferative activity than the other compounds. Two sulfonyl hydrazone derivatives 45 and 47 exhibited very good antioxidant activity. The results of anticholinesterase activity indicated that nine compounds 3, 8, 10, 14, 24, 25, 27, 38, and 45 significantly inhibited acetylcholinesterase enzymes and thirty-three compounds 1–4, 7–14, 22–28, 32–41, 44–47 inhibited butyrylcholinesterase enzymes (BChE) more than galantamine. In addition, virtual screening methods based on ligand 45 having the best activity against BChE was used to define new human BChE inhibitors. The interactions of ligand 8 against acetylcholinesterase (AChE) were also examined. Important key residues were determined and visualized on completion of the methodology. All calculations indicated the suitability of use of the molecular docking approach for understanding interaction mechanisms and crucial fragments of novel hit compounds such as the potential lead AChE and BChE inhibitor candidates.
- ?ztürk, Mehmet,Demirta?, Ibrahim,Iyido?an, Ay?egül Karakü?ük,Kur?un Aktar, Bedriye Seda,Oru?-Emre, Emine El?in,S?cak, Yusuf,Tok, Tu?ba Ta?k?n,Ya?l?o?lu, Ayse ?ahin
-
-
- The synthesis of sulfonated 4: H -3,1-benzoxazines via an electro-chemical radical cascade cyclization
-
A new route for the synthesis of sulfonated 4H-3,1-benzoxazines has been accomplished by electrochemical radical cascade cyclizations of styrenyl amides with sulfonylhydrazines. This process demonstrates a wide substrate scope with diverse functional group compatibility under metal- and external oxidant-free conditions at ambient temperature.
- He, Tian-Jun,Huang, Jing-Mei,Zhong, Wei-Qiang
-
supporting information
p. 2735 - 2738
(2020/03/17)
-
- A general and practical sulfonylation of benzylic ammonium salts with sulfonyl hydrazides for the synthesis of sulfones
-
A practical and efficient approach adopting transition-metal-free cross-coupling of sulfonyl hydrazides with benzyl ammonium salts has been developed to synthesize benzyl sulfones using Cs2CO3 as base under mild conditions. The protocol employs stable and easy to handle coupling partners, and is endowed with good substrate compatibility, leading to functional benzyl sulfones in good yields.
- Zhu, Haibo,Zhang, Yingying,Liu, Yishuai,Yang, Liu,Xie, Zongbo,Jiang, Guofang,Le, Zhang-Gao
-
supporting information
(2020/05/06)
-
- Synthesis of calix[4]azacrown substituted sulphonamides with antioxidant, acetylcholinesterase, butyrylcholinesterase, tyrosinase and carbonic anhydrase inhibitory action
-
A series of novel calix[4]azacrown substituted sulphonamide Schiff bases was synthesised by the reaction of calix[4]azacrown aldehydes with different substituted primary and secondary sulphonamides. The obtained novel compounds were investigated as inhibitors of six human (h) isoforms of carbonic anhydrases (CA, EC 4.2.1.1). Their antioxidant profile was assayed by various bioanalytical methods. The calix[4]azacrown substituted sulphonamide Schiff bases were also investigated as inhibitors of acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and tyrosinase enzymes, associated with several diseases such as Alzheimer, Parkinson, and pigmentation disorders. The new sulphonamides showed low to moderate inhibition against hCAs, AChE, BChE, and tyrosinase enzymes. However, some of them possessed relevant antioxidant activity, comparable with standard antioxidants used in the study.
- Akocak, Suleyman,Boga, Mehmet,Kalay, Erbay,Lolak, Nebih,Nocentini, Alessio,Oguz, Mehmet,Supuran, Claudiu T.,Yilmaz, Mustafa
-
p. 1215 - 1223
(2020/05/27)
-
- CuCl2-promoted decomposition of sulfonyl hydrazides for the synthesis of thiosulfonates
-
Sulfonyl hydrazides recently received much attention as reagents for the introduction of sulfur-containing functional groups into organic compounds, because both sulfonyl and sulfenyl sources could be generated by the oxidation and decomposition of the sulfonyl hydrazides, respectively. However, the transformations of sulfonyl hydrazides into thiosulfonates, which could be produced by the reaction between sulfonyl and sulfenyl sources, have been less investigated. In this manuscript, we describe CuCl2-promoted selective synthesis of thiosulfonates from sulfonyl hydrazides. A variety of thiosulfonates were produced in moderate to good yields. The mechanism involving radical intermediates such as sulfonyl radical and thiyl radical was proposed on the basis of the previously reported references and mechanistic investigations. In addition, quantum chemical simulations revealed that Cu-promoted decomposition of sulfonyl hydrazides is thermodynamically viable in the developed conditions.
- Kim, Junsu,Park, Sanggil,Kim, Hyungjun,Kim, Jinho
-
supporting information
(2020/07/02)
-
- An Alternative Metal-Free Aerobic Oxidative Cross-Dehydrogenative Coupling of Sulfonyl Hydrazides with Secondary Phosphine Oxides
-
An alternative metal-free, efficient and practical approach for the preparation of phosphinothioates is established via the aerobic oxidative cross-dehydrogenative coupling (CDC) of sulfonyl hydrazides with secondary phosphine oxides catalyzed by tetrabutylammonium iodide (TBAI) in the presence of atmospheric oxygen. The strategy provides an array of diverse phosphinothioates in good to excellent yields. Furthermore, two representative bioactive molecules are synthesized on up to gram scale by utilizing this method.
- Cheng, Feixiang,Liu, Jianjun,Liu, Teng,Yu, Rong,Zhang, Yanqiong
-
p. 253 - 262
(2019/12/28)
-
- Metal-Free Electrochemical Coupling of Vinyl Azides: Synthesis of Phenanthridines and β-Ketosulfones
-
We reported an efficient and environmentally benign electrochemical synthesis of phenanthridines by oxidative coupling of vinyl azides with sodium azide or benzenesulfonyl hydrazides, for the first time. The reaction conditions are mild, and no additional metal-catalyst or exogenous oxidants are needed. The protocol has broad substrate scope and high functional group tolerance. Furthermore, this green electrochemical procedure can be readily extended to the synthesis of β-ketosulfones. Gram scale reactions further demonstrate the practicability.
- Chen, Qianjin,Kong, Xianqiang,Li, Guodong,Liang, Qi,Lin, Long,Xu, Bo,Yu, Ke
-
supporting information
p. 6135 - 6145
(2020/10/06)
-
- One-pot synthesis of β-ketosulfones from sulfonyl chloride, hydrazine hydrate and vinyl azide in water
-
A novel, facile and efficient strategy for the one-pot synthesis of β-ketosulfones from readily available sulfonyl chloride, hydrazine hydrate and vinyl azides is described. The reaction proceeded very smoothly affording diverse β-ketosulfones in moderate to good yields. This new procedure has the advantages of environmental benign, easy and simple operation, low cost and wide tolerance of functional groups, which provides a highly fascinating protocol to access β-ketosulfones.
- Zhang, Yaohong,Luo, Mengqiang,Li, Yan,Shen, Runfu,Qi, Chenze,Wang, Hai,Cheng, Kai
-
supporting information
(2020/10/26)
-
- Structure based discovery of novel hexokinase 2 inhibitors
-
Hexokinase 2 (HK2) is over-expressed in most of human cancers and has been proved to be a promising target for cancer therapy. In this study, based on the structure of HK2, we screened over 6 millions of compounds to obtain the lead. A total of 26 (E)-N′-(2,3,4-trihydroxybenzylidene) arylhydrazide derivatives were then designed, synthesized, and evaluated for their HK2 enzyme activity and IC50 values against two cancer cell lines. Most of the 26 target compounds showed excellently in vitro activity. Among them, compound 3j showed the strongest inhibitory effects on HK2 enzyme activity with an IC50 of 0.53 ± 0.13 μM and exhibited the most potent growth inhibition against SW480 cells with an IC50 of 7.13 ± 1.12 μM, which deserves further studies.
- Chen, Lixia,Gao, Suyu,Li, Hua,Li, Mingxue,Li, Xingzhou,Liu, Yang,Wu, Canrong,Yang, Kaiyin,Zhang, Yujie,Zheng, Mengzhu
-
supporting information
(2020/02/04)
-
- Synergy of anodic oxidation and cathodic reduction leads to electrochemical deoxygenative C2 arylation of quinoline: N-oxides
-
The first example of electrochemical deoxygenative C2 arylation of quinoline N-oxides using sulfonyl hydrazines was demonstrated in this work. By employing both anodic oxidation and cathodic reduction, a variety of 2-arylquinolines were synthesized under metal catalyst-, exogenous-oxidant-, and exogenous-reductant-free conditions.
- Yuan, Yong,Jiang, Minbao,Wang, Tao,Xiong, Yunkui,Li, Jun,Guo, Huijiao,Lei, Aiwen
-
supporting information
p. 11091 - 11094
(2019/09/20)
-
- Synthesis of 3,4-Dihydrobenzo[f]phthalazines via Iodine/tert-Butyl Hydroperoxide-Mediated Annulation Cascade of Yne-Allenones
-
An iodine (I2)/tert-butyl hydroperoxide (TBHP)-mediated annulation cascade between yne-allenones and sulfonyl hydrazides has been established, in which a wide set of dihydrobenzo[f]phthalazines were synthesized through one-pot, two-step strategy under metal-free conditions. The synthetic utility of these transformations leads to subsequent C?C and C?N bond-forming reactions to effectively build up functional aza-heterocycle with potential significance. (Figure presented.).
- Fu, Rong,Li, Meng-Fan,Zhou, Peng,Hao, Wen-Juan,Tu, Shu-Jiang,Jiang, Bo
-
supporting information
p. 2280 - 2285
(2019/04/13)
-
- Palladium-Catalyzed Regio- and Stereoselective Sulfonylation of Aryl Propiolates with Sulfonyl Hydrazides: Access to (E)-β-Aryl Sulfonyl Acrylates
-
An efficient method for the synthesis of (E)-β-aryl sulfonyl acrylates has been reported. This palladium-catalyzed approach showed excellent regio- and stereoselectivity in the sulfonylation of aryl propiolates with sulfonyl hydrazides. Through this approach, a wide range of (E)-β-aryl sulfonyl acrylates were obtained in moderate to high yields. (Figure presented.).
- Jiang, Huanfeng,Yan, Wuxin,Huang, Jiuzhong,Tan, Chaowei,Zhan, Lingzhi,Wu, Wanqing
-
supporting information
p. 4575 - 4580
(2019/09/16)
-
- Exploration of Pd-catalysed four-component tandem reaction for one-pot assembly of pyrazolo[1,5-c]quinazolines as potential EGFR inhibitors
-
A series of pyrazolo[1,5-c]quinazolines as EGFR inhibitors was designed and synthesized by highly efficient and novel multicomponent route involving Pd-catalyzed tandem one-pot four-component reaction. The reaction proceeds with good functional group tolerance under a simple condition with excellent regioselectivity and high efficiency. Target compounds were screened against cancer cell lines MDA-MB-231, A549 and H1299. Of these, 9b and 10b exhibited superior anticancer activity (IC50 2.5 μM) to erlotinib and gefitinib. Synthetics were able to inhibit EGFR mediated kinase activity, induced ROS in cancer cells promoting mitochondrial mediated apoptosis via halting cell cycle progression at G1 phase.
- Ansari, Arshad J.,Joshi, Gaurav,Yadav, Umesh Prasad,Maurya, Antim K.,Agnihotri, Vijai K.,Kalra, Sourav,Kumar, Raj,Singh, Sandeep,Sawant, Devesh M.
-
-
- CHEMICAL COMPOUNDS AS ANTIBIOTICS
-
The invention relates to a compound which is an indane derivative according to Formula (I), or a pharmaceutically acceptable salt thereof, [FORMULA (I)] wherein R1, R2, R3, n, R4, p? q, L, ?, X and m are as defined herein. The compounds are useful in the treatment of antibacterial infection either as stand alone antibiotics, or in combination with further antibiotics. The compounds can also be used in vitro, for example in cleaning compositions.
- -
-
Page/Page column 117
(2018/10/19)
-
- Arylsulfonylhydrazone induced apoptosis in MDA-MB-231 breast cancer cells
-
Background: Breast cancer is the most frequent cancer among women. Chemotherapy is necessary for treating metastatic disease and represents an important therapeutic approach, although antineoplastic drugs have high toxicity and may be limited by the development of drug resistance. These problems impose an urgent need to discover new anticancer agents and, so, arylsulfonylhydrazone analogues were designed, synthesized, and evaluated with regard to their cytotoxic activity against breast cancer cells in order to identify novel potential antitumor agents. Methods: Synthesis was performed as previously described by Fernandes and co-workers. Cytotoxicity of sulfonylhydrazones against MDA-MB-231, MCF-7 and 3T3 cells was evaluated by MTT method. Apoptotic effects was verified by Annexin-V/PI assay, Hoechst stain and propidium iodide stain. Molecular modeling was executed using Spartan’10 version 1.1.0. Geometry optimization was performed by the MMFF, PM6 and Hartree-Fock 3-31G* methods and electronic and lipophilic properties were computed. Results: Thirteen analogues were synthesized, which 3f and 4f were cytotoxic against evaluated breast cancer cells. The most promising compound, 3f, showed IC50 values equal to 104.6 and 142.4 μM for MDA-MB-231 and MCF-7, respectively. 3f induced apoptosis, causing phosphatidylserine externalization, pyknosis, and cell cycle arrest in the G0/G1 phase in MDA-MB-231 breast cancer cells. Furthermore, 3f was selective for tumor cells when compared to 3T3 fibroblasts. Structure-activity relationship suggests that introduction of a benzodioxol group increased cytotoxicity and superior lipophilicity may be related to superior activity. Conclusion: Sulfonylhydrazone analogues presented good activity against breast cancer cells by inducing apoptosis and might be a promising scaffold to further molecular modifications persuing more effective antitumoral agents.
- Fernandes, Thais Batista,de Azevedo, Ricardo Alexandre,Yang, Rosania,Teixeira, Sarah Fernandes,Trossini, Gustavo Henrique Goulart,Barbuto, José Alexandre Marzag?o,Ferreira, Adilson Kleber,Parise-Filho, Roberto
-
p. 1288 - 1298
(2018/11/01)
-
- Benzoxazole-2-ethyl oxime derivate, preparation method and application thereof
-
The invention provides a benzoxazole-2-ethyl oxime derivate. The benzoxazole-2-ethyl oxime derivate is as shown in a formula (I) or a formula (II), wherein X1 and X2 are independently selected from NHor O; R1 and R3 are independently selected from H, F, Br or C1; R2 is selected from C1-C10 alkyl, substituted C1-C10 alkyl, phenyl or substituted phenyl; the substituted group of the substituted C1-C10 alkyl is selected from phenyl or halogen. Compared with the prior art, the benzoxazole-2-ethyl oxime derivate as shown in the formula (I) or the formula (II) is capable of obviously reducing anklejoint swelling degree and serum uric acid level of a rat with acute gouty arthritis, and is high in NLRP3 and TLR4 dual inhibition activity; the effect of the benzoxazole-2-ethyl oxime derivate is obviously prior to that of positive control dexamethasone; the benzoxazole-2-ethyl oxime derivate is applicable to preparation of drugs for treating hyperuricemia or acute gouty arthritis, and is small in side effect, and high in safety. (The formula is shown in the description).
- -
-
Paragraph 0190; 0191
(2018/03/24)
-
- Copper-mediated sulfonylation of aryl iodides and bromides with arylsulfonyl hydrazides in PEG-400
-
Sulfonylation using stable and readily available arylsulfonyl hydrazides and aryl iodides or bromides mediated by cupric acetate has been achieved. Using polyethylene glycol (PEG-400) as an eco-friendly medium, the coupling reaction could afford a series of unsymmetrical diaryl sulfones in moderate to good yields without the presence of additional ligands and base.
- Wu, Xiangmei,Wang, Yan
-
supporting information
p. 10953 - 10957
(2018/07/06)
-
- Exogenous-oxidant-free electrochemical oxidative C-H sulfonylation of arenes/heteroarenes with hydrogen evolution
-
An efficient and environmentally benign electrochemical oxidative radical C-H sulfonylation of arenes/heteroarenes was developed in this work. A series of significant diarylsulfones were prepared under mild catalyst- and exogenous-oxidant-free reaction conditions, which efficiently avoid the issues of desulfonylation or over-reduction of sulfonyl groups.
- Yuan, Yong,Yu, Yi,Qiao, Jin,Liu, Pan,Yu, Banying,Zhang, Wukun,Liu, Huilin,He, Min,Huang, Zhiliang,Lei, Aiwen
-
supporting information
p. 11471 - 11474
(2018/10/20)
-
- Diversity-Orientated Stereoselective Synthesis through Pd-Catalyzed Switchable Decarboxylative C?N/C?S Bond Formation in Allylic Surrogates
-
Switchable catalytic transformation of reactants can be a powerful approach towards diversity-orientated synthesis from easily available molecular synthons. Herein, an endogenous ligand-controlled, Pd-catalyzed allylic substitution allowing for either selective C?N or C?S bond formation using vinylethylene carbonates (VECs) and N-sulfonylhydrazones as coupling partners has been developed. This versatile methodology provides a facile, divergent route for the highly chemo- and stereoselective synthesis of functional allylic sulfones or sulfonohydrazides. The newly developed protocol features wide substrate scope (nearly 80 examples), broad functional group tolerance, and potential for the late-stage functionalization of bioactive compounds. The isolation and crystallographic analysis of a catalytically competent π-allyl Pd complex suggests that the pathway leading to the allylic products proceeds through a different manifold as previously proposed for the functionalization of VECs with nucleophiles.
- Deng, Lei,Kleij, Arjan W.,Yang, Weibo
-
supporting information
p. 19156 - 19161
(2018/11/30)
-
- Synthesis method of abiraterone acetate
-
The invention discloses a synthesis method of abiraterone acetate. The method includes: taking dehydroepiandrosterone as the raw material, conducting condensation with p-toluenesulfonhydrazide, then carrying out coupling reaction with 3-bromopyridine, and conducting acetylation so as to synthesize the target product abiraterone acetate. According to the synthesis method provided by the invention, the route has mild reaction conditions, the raw materials are cheap and easily available, and the production cost is low.
- -
-
Paragraph 0022; 0030; 0038
(2017/09/02)
-
- Gold-Catalyzed Dehydrazinative C(sp)–S Coupling Reactions of Arylsulfonyl Hydrazides with Ethynylbenziodoxolones for Accessing Alkynyl Sulfones
-
A gold(III)-catalyzed dehydrazinative coupling reaction between arylsulfonyl hydrazides and ethynylbenziodoxolone reagents was realized for the synthesis of alkynyl sulfones. The scope and versatility of the reaction were demonstrated by the efficient synthesis of 23 derivatives with diverse structural features.
- Shinde, Popat S.,Patil, Nitin T.
-
p. 3512 - 3515
(2017/07/04)
-