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Rapid routes of synthesis of oligonucleotide conjugates from non-protected oligonucleotides and ligands possessing different nucleophilic or electrophilic functional groups
Optimized methods are described for post-synthetic conjugation of non-protected oligodeoxyribonucleotides to different ligands. Methods for the terminal functionalization of oligonucleotides by amino, sulfhydryl, thiophosphate or carboxyl groups using dif
Grimm,Boutorine,Helene
p. 1943 - 1965
(2000)
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Design, synthesis, in vitro antiproliferative evaluation and in silico studies of new VEGFR-2 inhibitors based on 4-piperazinylquinolin-2(1H)-one scaffold
Angiogenesis is essential in the growth of solid tumors which need oxygen and nutrients supply to grow in size. The VEGF/VEGFR-2 signaling pathway plays an important role in tumor angiogenesis. Sorafenib is an FDA approved cancer therapeutic with activity
Abdelhamid, Dalia,Abourehab, Mohammed A. S.,Abuo‐Rahma, Gamal El‐Din A.,Badr, Mohamed,Hassan, Abdelfattah,Hassan, Heba A.
(2022/01/31)

N-Heterocyclic Carbene Catalyzed Ester Synthesis from Organic Halides through Incorporation of Oxygen Atoms from Air
Oxygenation reactions with molecular oxygen (O2) as the oxygen source provides a green and straightforward strategy for the construction of O-containing compounds. Demonstrated here is a novel N-heterocyclic carbene (NHC) catalyzed oxidative transformation of simple and readily available organic halides into valuable esters through the incorporation of O-atoms from O2. Mechanistic studies prove that the deoxy Breslow intermediate generated in situ is oxidized to a Breslow intermediate for further transformation by this oxidative protocol. This method broadens the field of NHC catalysis and promotes oxygenation reactions with O2.
Tan, Hui,Wang, Shen-An,Yan, Zixi,Liu, Jianzhong,Wei, Jialiang,Song, Song,Jiao, Ning
supporting information
p. 2140 - 2144
(2020/12/01)

Hesperetin derivative as well as synthesis method and application thereof
The invention relates to a hesperetin derivative as well as a synthesis method and application thereof. The hesperetin derivative disclosed by the invention has a chemical structural formula as shownin the figure. According to the invention, flavanone hes
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Paragraph 0026; 0030; 0033-0034

(2021/03/13)

Probing phenylcarbamoylazinane-1,2,4-triazole amides derivatives as lipoxygenase inhibitors along with cytotoxic, ADME and molecular docking studies
Hunting small molecules as anti-inflammatory agents/drugs is an expanding and successful approach to treat several inflammatory diseases such as cancer, asthma, arthritis, and psoriasis. Besides other methods, inflammatory diseases can be treated by lipoxygenase inhibitors, which have a profound influence on the development and progression of inflammation. In the present study, a series of new N-alkyl/aralky/aryl derivatives (7a-o) of 2-(4-phenyl-5-(1-phenylcarbamoyl)piperidine-4H-1,2,4-triazol-3-ylthio)acetamide was synthesized and screened for their inhibitory potential against the enzyme 15-lipoxygenase. The simple precursor ethyl piperidine-4-carboxylate (a) was successively converted into phenylcarbamoyl derivative (1), hydrazide (2), semicarbazide (3) and N-phenylated 5-(1-phenylcarbamoyl)piperidine-1,2,4-triazole (4), then in combination with electrophiles (6a-o) through further multistep synthesis, final products (7a-o) were generated. All the synthesized compounds were characterized by FTIR, 1H, 13C NMR spectroscopy, EIMS, and HREIMS spectrometry. Almost all the synthesized compounds showed excellent inhibitory potential against the tested enzyme. Compounds 7c, 7f, 7d, and 7g displayed potent inhibitory potential (IC50 9.25 ± 0.26 to 21.82 ± 0.35 μM), followed by the compounds 7n, 7h, 7e, 7a, 7b, 7l, and 7o with IC50 values in the range of 24.56 ± 0.45 to 46.91 ± 0.57 μM. Compounds 7c, 7f, 7d exhibited 71.5 to 83.5% cellular viability by MTT assay compared with standard curcumin (76.9%) when assayed at 0.125 mM concentration. In silico ADME studies supported the drug-likeness of most of the molecules. In vitro inhibition studies were substantiated by molecular docking wherein the phenyl group attached to the triazole ring was making a π-δ interaction with Leu607. This work reveals the possibility of a synthetic approach of compounds in relation to lipoxygenase inhibition as potential lead compounds in drug discovery.
Muzaffar, Saima,Shahid, Wardah,Riaz, Naheed,Saleem, Muhammad,Ashraf, Muhammad,Aziz-ur-Rehman,Bashir, Bushra,Kaleem, Ayesha,al-Rashida, Mariya,Baral, Bikash,Bhattarai, Keshab,Gross, Harald
(2020/12/21)

Synthesis and Antifungal Activity of New N-Aryl-2-(2-hydroxyphenylamino)ethylenediamine Derivatives
Abstract: In this study, a series of new N-aryl-2-(2-hydroxyphenylamino)ethylenediamine derivatives has beendesigned, synthesized and evaluated for antifungal activity against six selectedspecies of phytopathogenic fungi. Among the products, the most potent compoundhave demonstrated 97.7% inhibitory activity against S.sclerotiorum at the concentration of 50 μg/mL, which is higherthan that of the positive control chlorothalonil.
Gao, Han,Wan, Yichao,Tan, Yuhuan,Luo, Xi,Li, Lin
p. 122 - 127
(2021/02/21)

Structural basis of binding and justification for the urease inhibitory activity of acetamide hybrids of N-substituted 1,3,4-oxadiazoles and piperidines
In present, we have performed the Michaelis–Menten kinetics studies of urease inhibitors (6a–o), having basic skeleton of acetamide hybrids of N-substituted 1,3,4-oxadiazoles and piperidines. From the Lineweaver-Burk plot, Dixon plot and their secondary replots, it has been confirmed that all the compounds have inhibited the enzyme competitively with Ki values of in range from 3.11 ± 0.2 to 5.20 ± 0.7 μM. Compound 6a was found to have lowest Ki among the series, while compounds 6d, 6e, 6gand 6i were found subsequently the excellent Ki values after 6a. Molecular docking has supported their types of inhibitions and structure activity-relationship. Most frequently, the nitro group oxygen atoms were found in contact with nickel ions of the active site. Moreover, all the compounds were subjected to toxicity tests and were found nontoxic against human neutrophils and plants, respectively.
Abbasi, Muhammad Athar,Afridi, Sahib Gul,Khan, Ajmal,Khan, Asifullah,Khan, Farman Ali,Lodhi, Muhammad Arif,Rehman, Aziz Ur
(2020/09/18)

Design, synthesis, anticancer and antioxidant activities of amide linked 1,4-disubstituted 1,2,3-triazoles
To explore anticancer and antioxidant agents with improved potency, we synthesized a series of amide linked 1,4-disubstituted 1,2,3-triazoles through click chemistry approach. The structure of synthesized triazoles were characterized by- FTIR, 1H NMR, 13C NMR spectroscopy and HRMS. All the synthesized compounds were screened for their anticancer activity against four different cell lines- PC3 (prostate cancer), A549 (lung cancer), MIAPACA (liver cancer), Fr2 (Breast epithelial), reflecting compounds 7e and 7f to possess good activity. The antioxidant activity was evaluated by using stable free radical 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay and compound 7d showed promising activity having IC50 value 1.61 μg/ml. Molecular docking studies of compounds 7e and 7f was carried out in active site of human epidermal growth factor receptor 2 revealed high binding affinities and within toxicity limits. The experimental results were in good agreement with docking studies. In-silico ADME studies of synthesized compounds also have good dispositional profile and are patient compliant, may be potential future candidates for anticancer treatment.
Das, Ashutosh,Kaushik, C. P.,Kumar, Ashwani,Kumar, Deepak,Kumar, Devinder,Luxmi, Raj,Sangwan, Jyoti,Singh, Dharmendra
(2020/10/08)

Pyrazoline tethered 1,2,3-triazoles: Synthesis, antimicrobial evaluation and in silico studies
A new series of pyrazoline-amide linked 1,2,3-triazole hybrids was wisely designed and synthesized using 1,3-dipolar cycloaddition between pyrazoline linked alkynes and 2-bromo-N-arylacetamide. All the newly synthesized compounds were evaluated in vitro against different microbial strains viz. Escherichia coli, Bacillius subtilis, Staphylococcus aureus, Aspergillus niger, and Candida albicans. Pyrazoline linked terminal alkynes (4a–c) showed MIC = 0.062–0.078 μmol/mL against different bacterial and fungal strain. However, pyrazoline-amide linked 1,2,3-triazole hybrids (6a-6t) showed MIC = 0.0229–0.050 μmol/mL. Compound 6e exhibited better efficacy against E. coli and both the fungal strains compared to standard drugs used. Docking studies of the most potent compounds were carried out against bacterial DNA Gyr A and fungal 14α-steroldemethylase were also performed. The binding potential of 4a and 6e with both the target using molecular dynamics simulations was also investigated.
Kumar, Anil,Kumar, Ashwani,Kumar, Lokesh,Lal, Kashmiri,Paul, Avijit Kumar
(2021/08/03)

New 3-(1H-benzo[d]imidazol-2-yl)quinolin-2(1H)-one-based triazole derivatives: Design, synthesis, and biological evaluation as antiproliferative and apoptosis-inducing agents
A series of 1,2,3-triazole derivatives based on the quinoline–benzimidazole hybrid scaffold was designed, synthesized, and screened against a panel of NCI-60 humanoid cancer cell lines for in vitro cytotoxicity evaluation, which revealed that compound Q6 was the most potent cytotoxic agent with excellent GI50, TGI, and LC50 values on multiple cancer cell lines. Q6 was tested further on the BT-474 breast cancer line to evaluate the mechanism of action. Preliminary screening studies based on the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay revealed that compound Q6 had an excellent antiproliferative effect against human breast cancer cells, BT-474, with IC50 values of 0.59 ± 0.01 μM. The detailed study based on the acridine orange/ethidium bromide staining (AO/EB) and the 4′,6-diamidino-2-phenylindole (DAPI) assay suggested that the antiproliferative activity shown was due to the induction of apoptosis on exposure to Q6. Further, DCFDA staining showed the generation of reactive oxygen species, altering the mitochondrial potential and leading to the initiation of apoptosis. This was further supported by JC-1 staining, indicating that this scaffold can contribute to the development of more potent derivatives.
Gaikwad, Nikhil B.,Bansode, Sapana,Biradar, Shankar,Ban, Mayuri,Srinivas, Nanduri,Godugu, Chandraiah,Yaddanapudi, Venkata M.
(2021/08/07)

Discovery of Novel Acetamide-Based Heme Oxygenase-1 Inhibitors with PotentIn VitroAntiproliferative Activity
Heme oxygenase-1 (HO-1) promotes heme catabolism exercising cytoprotective roles in normal and cancer cells. Herein, we report the design, synthesis, molecular modeling, and biological evaluation of novel HO-1 inhibitors. Specifically, an amide linker in the central spacer and an imidazole were fixed, and the hydrophobic moiety required by the pharmacophore was largely modified. In many tumors, overexpression of HO-1 correlates with poor prognosis and chemoresistance, suggesting the inhibition of HO-1 as a possible antitumor strategy. Accordingly, compounds7iand7l-pemerged for their potency against HO-1 and were investigated for their anticancer activity against prostate (DU145), lung (A549), and glioblastoma (U87MG, A172) cancer cells. The selected compounds showed the best activity toward U87MG cells. Compound7lwas further investigated for its in-cell enzymatic HO-1 activity, expression levels, and effects on cell invasion and vascular endothelial growth factor (VEGF) extracellular release. The obtained data suggest that7lcan reduce cell invasivity acting through modulation of HO-1 expression.
Fallica, Antonino N.,Sorrenti, Valeria,D’Amico, Agata G.,Salerno, Loredana,Romeo, Giuseppe,Intagliata, Sebastiano,Consoli, Valeria,Floresta, Giuseppe,Rescifina, Antonio,D’Agata, Velia,Vanella, Luca,Pittalà, Valeria
p. 13373 - 13393
(2021/09/20)

Identification of phenylcarbamoylazinane-1,3,4-oxadiazole amides as lipoxygenase inhibitors with expression analysis and in silico studies
In search for new anti-inflammatory agents that inhibit the enzymes of arachidonic acid pathway as the drug targets, the present article describes the screening of 1,3,4-oxadiazole analogues against lipoxygenase (LOX) enzyme. The work is based on the synthesis of new N-alkyl/aralky/aryl derivatives (6a-o) of 2-(4-phenyl-5-(1-phenylcarbamoylpiperidine)-4H-1,3,4-oxadiazol-3-ylthio)acetamide which were obtained by the reaction of 1,3,4-oxadiazole (3) with various electrophiles (5a-o), in KOH. The synthesized analogues showed potent to moderate inhibitory activity against the soybean 15-LOX enzyme; especially 6g, 6b, 6a and 6l displayed the potent inhibitory potential with IC50 values 7.15 ± 0.26, 9.32 ± 0.42, 15.83 ± 0.45 & 18.37 ± 0.53 μM, respectively, while excellent to moderate inhibitory profiles with IC50 values in the range of 26.13–98.21 μM were observed from the compounds 6k, 6m, 6j, 6o, 6h, 6f, 6n and 6c. Most of the active compounds exhibited considerable cell viability against blood mononuclear cells (MNCs) at 0.25 mM by MTT assay except 6f, 6h, 6k and 6m which showed around 50% cell viability. Flow cytometry studies of the selected compounds 6a, 6j and 6n revealed that these caused 79.5–88.51% early apoptotic changes in MNCs compared with 4.26% for control quercetin at their respective IC50 values. The relative expression of 5-LOX gene was monitored in MNCs after treatment with these three molecules and all down-regulated the enzyme activity. In silico ADME and molecular docking studies further supported these studies of oxadiazole derivatives and considered it as potential ‘lead’ compounds in drug discovery and development.
Amjad, Hira,Ashraf, Muhammad,Aziz-ur-Rehman,Bashir, Bushra,Bhattarai, Keshab,Imran, Muhammad,Muzaffar, Saima,Riaz, Naheed,Saleem, Muhammad,Shahid, Wardah
(2021/08/19)

Structure–activity relationship and biological evaluation of 12 N-substituted aloperine derivatives as PD-L1 down-regulatory agents through proteasome pathway
Twenty-nine 12 N-substituted aloperine derivatives were synthesized and screened for suppression on PD-L1 expression in H460 cells, as a continuation of our work. Systematic structural modifications led to the identification of compound 6b as the most act
Zeng, Qing–Xuan,Wang, Kun,Zhang, Xin,Shi, Yu-Long,Dou, Yue–Ying,Guo, Zhi–Hao,Zhang, Xin–Tong,Zhang, Na,Deng, Hong–Bin,Li, Ying–Hong,Song, Dan–Qing
(2021/10/22)

Catalyst-free generation of acyl radicals induced by visible light in water to construct C-N bonds
We describe herein a catalyst-free and redox-neutral photochemical strategy for the direct generation of acyl radicals from α-diketones, and its selective conversion of nitrosoarenes to hydroxyamides or amides with AcOH or NaCl as an additive. The reaction was carried out under mild conditions in water with purple LEDs as the light source. A broad scope of substrates was demonstrated. Mechanistic experiments indicate that α-diketones cleave to give acyl radicals, with hydroxyamides being further reduced to amides.
Ran, Maogang,He, Jiaxin,Yan, Boyu,Liu, Wenbo,Li, Yi,Fu, Yunfen,Li, Chao-Jun,Yao, Qiuli
supporting information
p. 1970 - 1975
(2021/03/16)

Toward two-photon absorbing dyes with unusually potentiated nonlinear fluorescence response
The combination of two two-photon-induced processes in a F?rster resonance energy transfer (FRET)-operated photochromic fluorene-dithienylethene dyad lays the foundation for the observation of a quartic dependence of the fluorescence signal on the excitat
Benitez-Martin, Carlos,Li, Shiming,Dominguez-Alfaro, Antonio,Najera, Francisco,Pérez-Inestrosa, Ezequiel,Pischel, Uwe,Andréasson, Joakim
supporting information
p. 14854 - 14858
(2020/10/13)

Antitubercular and Antiparasitic 2-Nitroimidazopyrazinones with Improved Potency and Solubility
Following the approval of delamanid and pretomanid as new drugs to treat drug-resistant tuberculosis, there is now a renewed interest in bicyclic nitroimidazole scaffolds as a source of therapeutics against infectious diseases. We recently described a nitroimidazopyrazinone bicyclic subclass with promising antitubercular and antiparasitic activity, prompting additional efforts to generate analogs with improved solubility and enhanced potency. The key pendant aryl substituent was modified by (i) introducing polar functionality to the methylene linker, (ii) replacing the terminal phenyl group with less lipophilic heterocycles, or (iii) generating extended biaryl side chains. Improved antitubercular and antitrypanosomal activity was observed with the biaryl side chains, with most analogs achieved 2- to 175-fold higher activity than the monoaryl parent compounds, with encouraging improvements in solubility when pyridyl groups were incorporated. This study has contributed to understanding the existing structure-activity relationship (SAR) of the nitroimidazopyrazinone scaffold against a panel of disease-causing organisms to support future lead optimization.
Ang, Chee Wei,Tan, Lendl,Sykes, Melissa L.,Abugharbiyeh, Neda,Debnath, Anjan,Reid, Janet C.,West, Nicholas P.,Avery, Vicky M.,Cooper, Matthew A.,Blaskovich, Mark A. T.
p. 15726 - 15751
(2020/12/02)

Selective carbonic anhydrase inhibitor, synthesis method and application thereof
The invention discloses a selective carbonic anhydrase inhibitor. The compound adopts acetazolamide as a lead compound, and is designed and synthesized by introducing a side chain for structural modification. The structure comprises a monosubstituted compound and a disubstituted compound; the selective inhibition effect of the compound on carbonic anhydrase is evaluated by esterase method; the neuroprotective effect of the compound is evaluated through a sodium nitroprusside oxidative stress model; and the toxicity of the compound is tested through cytotoxicity experiment. Research results show that in terms of the inhibition effect of the compound on carbonic anhydrase, monosubstitution is superior to disubstitution; the selectivity to carbonic anhydrase II is superior to that of carbonicanhydrase IX; the monosubstituted compound presents certain protective effect on sodium nitroprusside damaged PC12 cells; the IC50 of the optimal compound to carbonic anhydrase II is 16.7nM, the IC50to carbonic anhydrase IX is 4757nM, the selectivity is 285 times, which is remarkably superior to that of acetazolamide; the neuroprotective effect on PC12 is close to that of acetazolamide, and thetoxicity is lower than that of acetazolamide. The compound has the characteristics of good selectivity, effectiveness and safety, and is expected to be applied to drugs for preventing and treating neurological diseases.
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Paragraph 0096; 0098

(2020/03/06)

5-[2-(N-(Substituted phenyl)acetamide)]amino-1,3,4-thiadiazole-2-sulfonamides as Selective Carbonic Anhydrase II Inhibitors with Neuroprotective Effects
In this study, 22 novel compounds were designed and synthesized by acetamide bridge chains, among which 5 a–5 k were monosubstituted compounds, and 6 a–6 k were disubstituted. A series of biological evaluations was then carried out to determine the carbonic anhydrase inhibitory activity, neuroprotective effects and cytotoxicity of 5 a–5 k and 6 a–6 k. The results showed that some compounds could protect PC12 cells from sodium nitroprusside (SNP)-induced damage. In terms of the neuroprotection and inhibitory activity against carbonic anhydrase II, monosubstituted compounds were better than disubstituted. Compound 5 c exhibited better protective effect in PC12 cells than that of edaravone, and 5 c also showed less cytotoxicity. In addition, compound 5 c was found to be the most effective selective carbonic anhydrase II inhibitor (IC50=16.7 nM, CAI/CAII=54.3), which was similar to the inhibitory effect of acetazolamide. Moreover, the selectivity of compound 5 c was better than that of acetazolamide (IC50=12.0 nM, CAI/CAII=20.8). Molecular docking presented that the binding effect of compound 5 c with carbonic anhydrase II was superior to that of 5 c with carbonic anhydrase I and IX, which was consistent with the inhibitory results. Based on above findings, compound 5 c may be a potential candidate for selective carbonic anhydrase II inhibitor, and it had obviously neuroprotective effect and great advantages in drug safety.
Jiang, Caibao,Lao, Yaoqiang,Liao, Liping,Liu, Jiayong,Shi, Jinguo,Wang, Yang,Zhang, Jingxia,Zhang, Liantao
(2020/03/24)

Design, synthesis of novel (Z)-2-(3-(4-((3-benzyl-2,4-dioxothiazolidin-5-ylidene)methyl)-1-phenyl-1H-pyrazol-3-yl)phenoxy)-N-arylacetamide derivatives: Evaluation of cytotoxic activity and molecular docking studies
In an attempt to discover potential cytotoxic agents, a series of novel (Z)-2-(3-(4-((3-benzyl-2,4-dioxothiazolidin-5-ylidene)methyl)-1-phenyl-1H-pyrazol-3-yl) phenoxy)-N-arylacetamide derivatives 11a-n were synthesized in varied steps with acceptable reaction procedures with good yields and characterized by 1H NMR, 13C NMR, IR and ESI-MS spectra. All the novel synthesized derivatives were assessed for their cytotoxic activity against human breast cell line (MCF-7) with different concentration of 0.625 μM, 1.25 μM, 2.5 μM, 5 μM and 10 μM respectively. Biological evaluation assay results were displayed in terms of percentage of cell viability reduction and IC50 values. Most of the screened derivatives demonstrated moderate to promising cytotoxic activity. Some of the derivatives, particularly compound 11d and 11n have shown promising cytotoxic activity with IC50 values 0.604 μM and 0.665 μM compared to standard drug cisplatin and compounds 11a, 11e and 11g also have shown considerable cytotoxic activity and the rest of the derivatives have shown moderate activity. Furthermore, molecular docking calculations and ADME properties of the synthesized molecules are in effective compliance with the cytotoxic evaluation results.
Kolluri, Prashanth Kumar,Gurrapu, Nirmala,Subhashini,Putta, Shravani,Singh, Surya Sathyanarayana,Vani, Tamalapakula,Manga, Vijjulatha
(2019/11/26)

A novel method for the synthesis of 1,2,4-triazole-derived heterocyclic compounds: enzyme inhibition and molecular docking studies
Two series of new N-aryl/aralkyl derivatives (9a–q) of 2-(4-ethyl-5-(thiophen-2-ylmethyl)-4H-1,2,4-triazol-3-ylthio)acetamide and N-aryl/aralkyl derivatives (10a–q) of 2-(4-phenyl-5-(thiophen-2-ylmethyl)-4H-1,2,4-triazol-3-ylthio)acetamide were synthesized. The methods included successive conversions of thiophen-2-acetic acid (a) into its respective ester, hydrazide and N-aryl/aralkyl 1,3,4-triazole. The target compounds (9a–q; 10a–q) were obtained by the reaction of N-aryl/aralkyl 1,3,4-triazole (5, 6) with various electrophiles, (8a–q), in N,N-dimethyl formamide (DMF) and sodium hydroxide at room temperature. The characterization of these compounds was done by FTIR, 1H-, 13C-NMR, EI-MS and HR-EI-MS spectral data. All compounds were evaluated for their enzyme inhibitory potentials against electric eel acetylcholinesterase, AChE (10f, 10d; IC50 values 32.26 ± 0.12, 45.72 ± 0.11?μM, respectively), equine butyrylcholinesterase, BChE (9d, 9l, 9b, 10d, 10h; IC50 values 12.52 ± 0.19, 12.52 ± 0.19, 21.72 ± 0.18, 23.62 ± 0.22, 24.52 ± 0.21?μM, respectively), jack bean urease (10i, 10n, 9e; IC50 values 7.27 ± 0.05, 7.35 ± 0.04, 8.79 ± 0.05?μM, respectively) and yeast α-glucosidase enzymes (9o, 10i; IC50 values 62.94 ± 0.19, and 69.46 ± 0.15?μM, respectively). The molecular docking studies supported these findings. This study provides cheaper bioactive triazole amides as promising future lead molecules.
Riaz, Naheed,Iftikhar, Muhammad,Saleem, Muhammad,Aziz-ur-Rehman,Ahmed, Ishtiaq,Ashraf, Muhammad,Shahnawaz,Rehman, Jameel,al-Rashida, Mariya
p. 1183 - 1200
(2020/01/31)

Synthesis, anticancer, and computational studies of 1, 3, 4-oxadiazole-purine derivatives
Theophylline-7-acetic acid (acefylline) (3) and its derivatives are pharmacologically active compounds and generally recognized as bronchodilators for the treatment of respiratory diseases like acute asthma for over 70 years. In this article, synthesis of
Faisal, Shahla,Kamal, Shagufta,Parveen, Bushra,Rasool, Nasir,Rasul, Azhar,Raza, Zohaib,Shahzadi, Irum,Zahid, Faisal M.,Zahoor, Ameer F.,Zia-ur-Rehman, Muhammad
p. 2782 - 2794
(2020/04/16)

Convergent synthesis, free radical scavenging, Lineweaver-Burk plot exploration, hemolysis and in silico study of novel indole-phenyltriazole hybrid bearing acetamides as potent urease inhibitors
In the current paper, through a convergent multi-step approach, a library of novel indole-phenyltriazole hybrids containing an amide moiety (9a-k) was synthesized. The structural verification of all synthesized molecules was accomplished by CHN and spectral analyses data. These synthesized bi-heterocyclic derivatives (9a-k) were evaluated for their anti-ulcer potential by inhibitory action against Jack bean urease enzyme and subsequently their structure-activity relationship was perceived. Moreover, these compounds were inspected for cytotoxic profile by hemolytic activity and it was professed that nearly all the synthesized compounds showed low cytotoxicity. In addition, free radical scavenging activity and kinetic analysis were also carried out for these compounds to understand their mode of inhibition. So, it was summated that these derivatives might lead to further research gateways for obtaining better and safe anti-ulcer agents.
Abbasi, Muhammad A.,Ali Shah, Syed A.,Hassan, Mubashir,Khan, Wajiha,Nazir, Majid,Raza, Hussain,Rehman, Aziz-ur,Seo, Sung Y.,Shahid, Muhammad,Siddiqui, Sabahat Z.
(2020/05/25)

Synthesis and antidiabetic evaluation of benzimidazole-tethered 1,2,3-triazoles
Some novel benzimidazole-tethered 1,2,3-triazole derivatives (4a–r) were synthesized by a click reaction between 2-substituted 1-(prop-2-yn-1-yl)-1H-benzo[d]imidazole and in situ azide. The structures of the synthesized compounds were confirmed by spectroscopic studies (one- and two-dimensional nuclear magnetic resonance, Fourier transform infrared, and high-resolution mass spectra). The synthesized compounds were evaluated for their antidiabetic activity. Compounds 4a–r exhibited a good-to-moderate α-amylase and α-glucosidase inhibitory activity, with IC50 values ranging from 0.0410 to 0.0916 μmol/ml and 0.0146 to 0.0732 μmol/ml, respectively. Compounds 4e, 4g, and 4n were found to be most active. Furthermore, the binding conformation of the most active compounds was ascertained by docking studies.
Deswal, Laxmi,Verma, Vikas,Kumar, Devinder,Kaushik, Chander?P.,Kumar, Ashwani,Deswal, Yogesh,Punia, Suman
(2020/07/04)

Synthesis of Novel Bi-Heterocycles as Valuable Anti-Diabetic Agents: 2-({5-((2-Amino-1,3-Thiazol-4-yl)methyl)-1,3,4-Oxadiazol-2-yl}sulfanyl)-N-(Substituted)acetamides
Abstract: The synthesis of a new series of S-substituted acetamides derivatives of 5-[(2-amino-1,3-thiazol-4-yl)methyl]-1,3,4-oxadiazol-2-thiol were synthesized and evaluated for enzyme inhibition study along with cytotoxic behavior. Ethyl 2-(2-amino-1,3-thiazol-4-yl)acetate was converted to corresponding acid hydrazide by hydrazine hydrate in ethanol. The reflux of acid hydrazide with carbon disulfide resulted to 5-[(2-amino-1,3-thiazol-4-yl)methyl]-1,3,4-oxadiazol-2-thiol. Different electrophiles were synthesized by the reaction of respective anilines (one in each reaction) and 2-bromoacetylbromide in an aqueous medium. The targeted bi-heterocyclic compounds were synthesized by stirring nucleophilic 5-[(2-amino-1,3-thiazol-4-yl)methyl]-1,3,4-oxadiazol-2-thiol with different acetamides electrophiles (one after another), in DMF using LiH as base and activator. The proposed structures of newly synthesized compounds were deduced by spectroscopic techniques such as 1H NMR, 13C NMR, EI MS and elemental analysis. These novel bi-heterocycles were tested for their anti-diabetic potential via the in vitro inhibition of α-glucosidase enzyme. The in silico study of these molecules was also coherent with their enzyme inhibition data. Furthermore, these molecules were analyzed for their cytotoxic behavior against brine shrimps. It was inferred from the results that most of them exhibited very potent inhibitory potential against the studied enzyme and can be utilized as valuable anti-diabetic agent.
Aziz-ur-Rehman,Khan, Farman Ali,Lodhi, Muhammad Arif,Mirza, Bushra,Muhammad, Athar Abbasi,Ramzan, Muhammad Shahid,Shah, Syed Adnan Ali,Siddiqui, Sabahat Zahra
p. 590 - 598
(2020/10/02)

Synthesis of Oxindole Derivatives via Intramolecular C–H Insertion of Diazoamides Using Ru(II)-Pheox Catalyst
This work presented the efficient intramolecular aromatic C–H insertion of diazoacetamide. The 1a–1o diazo compounds (except for 1k) were converted into their corresponding oxindoles via an intramolecular C–H insertion reaction in the presence of a Ru catalyst. The Ru-Pheox catalyst was shown to be highly efficient in this transformation in terms of the regioselectivity, producing the desired products in excellent yield (99%). The efficiency of the Ru catalyst reached 580 (TON) and 156 min?1 (TOF).
Phan Thi Thanh, Nga,Dang Thi Thu, Huong,Tone, Masaya,Inoue, Hayato,Iwasa, Seiji
(2020/10/02)

Microwave-assisted synthesis and luminescent activity of imidazo[1,2-a]pyridine derivatives
In this work, a series of phenacyl bromide derivatives was synthesized and employed as key intermediate for the synthesis of substituted imidazo[1,2-a]pyridines. First, phenacyl bromide molecules were obtained from the bromination reaction of acetophenones assisted by microwave irradiation, obtaining the products 4a-v in a 15 minutes reaction with yields in the range of 50% to 99%. Subsequently, the conjugation of these molecules with 2-aminopyridine conduced to the production of imidazo[1,2-a]pyridine derivatives (7a-v) in a 60-second reaction with yields of 24% to 99%. Improved yields were determined with respect to those obtained with more tedious methodologies like thermally and mechanically assisted routes. Intense luminescence emissions in the purple and blue regions of the electromagnetic spectra were observed under UV excitation according to the nature of the substituents. This environmentally friendly methodology is expected to constitute an important class of organic compounds for the development of biomarkers, photochemical sensors, and medicinal applications.
Rodríguez, Juan C.,Maldonado, Rony A.,Ramírez-García, Gonzalo,Díaz Cervantes, Erik,de la Cruz, Fabiola N.
p. 2279 - 2287
(2020/03/16)

Amide-Based Cinchona Alkaloids as Phase-Transfer Catalysts: Synthesis and Potential Application
Herein we present a library of simple amide derivatives of Cinchona alkaloids in the form of quaternary ammonium salts. The obtained derivatives can be generated very easily and efficiently from inexpensive and commercially available substrates. We tested this class of alkaloids in the alkylation of glycine derivative, carried out under phase-transfer catalyst conditions. The presented hybrid catalysts offer both high reaction yields (up to 97%) and high enantioselectivities of the obtained product (up to 94% ee).
Majdecki, Maciej,Niedbala, Patryk,Jurczak, Janusz
supporting information
p. 8085 - 8090
(2019/10/14)

Synthesis and structure-activity relationship of tyrosinase inhibiting novel bi-heterocyclic acetamides: Mechanistic insights through enzyme inhibition, kinetics and computational studies
The present research was designed for the selective synthesis of novel bi-heterocyclic acetamides, 9a-n, and their tyrosinase inhibition to overwhelm the problem of melanogenesis. The structures of newly synthesized compounds were confirmed by spectral techniques such as 1H NMR, 13C NMR, and EI-MS along with elemental analysis. The inhibitory effects of these bi-heterocyclic acetamides (9a-n) were evaluated against tyrosinase and all these molecules were recognized as potent inhibitors relative to the standard used. The Kinetics mechanism was analyzed by Lineweaver-Burk plots which explored that compound, 9h, inhibited tyrosinase competitively by forming an enzyme-inhibitor complex. The inhibition constants Ki calculated from Dixon plots for this compound was 0.0027 μM. The computational study was coherent with the experimental records and these ligands exhibited good binding energy values (kcal/mol). The hemolytic analysis revealed their mild cytotoxicity towards red blood cell membranes and hence, these molecules can be pondered as nontoxic medicinal scaffolds for skin pigmentation and related disorders.
Butt, Abdul Rehman Sadiq,Abbasi, Muhammad Athar,Aziz-ur-Rehman,Siddiqui, Sabahat Zahra,Raza, Hussain,Hassan, Mubashir,Shah, Syed Adnan Ali,Shahid, Muhammad,Seo, Sung-Yum
p. 459 - 472
(2019/02/19)

Design, synthesis, fungicidal activity and molecular docking studies of novel 2-((2-hydroxyphenyl)methylamino)acetamide derivatives
A series of novel 2-hydroxyphenyl substituted aminoacetamides was designed by molecular hybridization of the aminoacetamide scaffold and 2-hydroxyphenyl motif. The target compounds were synthesized and their fungicidal activities were evaluated. Some of the target compounds showed excellent antifungal activities against S. sclerotiorum and P. capsici. Significantly, compounds 5e displayed the most potent activity against S. sclerotiorum with EC50 = 2.89 μg/mL, which was lower than that of commercial chlorothalonil. The systematic studies provided strong confidence that the hydroxyl group and the carbonyl group are crucial for the fungicidal activity. Molecular docking studies suggest that SDH enzyme could be one of the potential action targets of our compounds.
Tang, Zilong,Li, Xinxing,Yao, Yuan,Qi, Yongcun,Wang, Ming,Dai, Ningning,Wen, Yuhao,Wan, Yichao,Peng, Lifen
p. 2572 - 2578
(2019/03/26)

Efficient synthesis, antitubercular and antimicrobial evaluation of 1,4-disubstituted 1,2,3-triazoles with amide functionality
Abstract: A series of 21 amide linked 1,4-disubstituted-1,2,3-triazoles were achieved via one-pot synthesis through Cu(I) catalyzed click reaction between terminal alkynes and 2-azido-N-substituted acetamides. Newly formed triazoles were characterized by various spectroscopic techniques (FT-IR, 1H NMR, 13C NMR spectroscopy, and HRMS) and investigated for in vitro antitubercular evaluation against bacteria, i.e., Mycobacterium tuberculosis and antimicrobial evaluation against Bacillus subtilis, Staphylococcus epidermidis, Escherichia coli, Pseudomonas aeruginosa, Candida albicans, and Aspergillus niger. Some of the synthesized triazole derivatives were found to exhibit moderate inhibitory activity against the tested antitubercular strain, whereas one compound displayed a significant inhibitory activity against most of the tested microbial strains. Graphical abstract: [Figure not available: see fulltext.].
Kaushik,Pahwa, Ashima,Singh, Dharmendra,Kumar, Krishan,Luxmi, Raj
p. 1127 - 1136
(2019/05/28)

One-pot facile synthesis, crystal structure and antifungal activity of 1,2,3-triazoles bridged with amine-amide functionalities
A library of twenty five 1,2,3-triazoles bridged with amine-amide functionalities have been synthesized from reaction of N-substituted(prop-2-yn-1-yl)amines (2a–2e), 2-bromo-N-arylacetamides (4a–4e) and sodium azide through copper(I)-catalyzed alkyne-azide cycloaddition. The synthesized compounds were characterized by using FTIR, 1H NMR, 13C NMR, and HRMS techniques. The structures of synthesized 5a (CCDC 1569245) and 5h (CCDC 1569249) were also confirmed by X-ray crystallography. Antifungal evaluation of newly synthesized triazoles was carried out against–Candida albicans and Aspergillus niger. Biological screening of synthesized 1,2,3-triazoles revealed moderate to good antifungal activity against tested strains.
Kaushik,Luxmi, Raj,Kumar, Mukesh,Singh, Dharmendra,Kumar, Krishan,Pahwa, Ashima
supporting information
p. 118 - 128
(2019/01/24)

Synthesis, crystal structure and antimicrobial activity of 2-((2-(4-(1H-1,2,4-triazol-1-yl)phenyl)quinazolin-4-yl)oxy)-N-phenylacetamide derivatives against phytopathogens
Abstract: A total of eighteen 2-((2-(4-(1H-1,2,4-triazol-1-yl)phenyl)quinazolin-4-yl)oxy)-N-phenylacetamide derivatives were designed and synthesized, via hybrid pharmacophore approach. Among these compounds, chemical structure of compound 4a was unambiguously confirmed by means of single-crystal X-ray diffraction analysis. All the compounds were evaluated in vitro for their inhibition activity against several important phytopathogenic bacteria and fungi in agriculture. The obtained results indicated that several compounds demonstrated potent antibacterial activity against Xanthomonas oryzae pv. oryzae (Xoo). For example, compounds 4c, 4g and 4q had EC50 values of 35.0, 36.5 and 32.4 μg/mL toward this bacterium, respectively, around 1.5 times more active than commercial bactericide bismerthiazol (EC50 = 89.8 μg/mL). Additionally, compounds 4j and 4p were found to display comparable antifungal activity against Gloeosporium fructigenum at 50 μg/mL, to commercial fungicide hymexazol. Finally, the relationships between antibacterial activities and molecular structures of this class of compounds were discussed in detail. Graphical abstract: [Figure not available: see fulltext.].
Fan, Zhijiang,Shi, Jun,Luo, Na,Bao, Xiaoping
p. 615 - 624
(2019/08/12)

12N-substituted matrinol derivatives inhibited the expression of fibrogenic genes via repressing integrin/FAK/PI3K/Akt pathway in hepatic stellate cells
Twenty new 12N-substituted matrinol derivatives were synthesized and evaluated for their inhibitory effects on collagen α1 (I) (COL1A1) promotor in human hepatic stellate LX-2 cells. The structure-activity relationship (SAR) revealed that introducing a 12N-benzeneaminoacylmethyl substitution might significantly enhance the activity. Compound 8a exhibited the highest inhibitory potency against COL1A1, and its inhibition activity against COL1A1 was further confirmed on both the mRNA and protein levels. It also effectively inhibited the expression of α smooth muscle actin (α-SMA), fibronectin and transforming growth factor β1 (TGFβ1), indicating an extensive inhibitory effect on the expression of fibrogenic genes. The primary mechanism study indicated that it might take action via the Integrin/FAK/PI3K/Akt signaling pathway. The results provided powerful information for further structure optimization, and compound 8a was selected as a novel anti-fibrogenic lead for further investigation.
Bao, Yunyang,Pang, Yudong,Tang, Sheng,Niu, Tianyun,Guo, Zhihao,He, Hongwei,Li, Yinghong,Song, Danqing
(2019/10/28)

Design, Synthesis, Antimicrobial Evaluation, and Laccase Catalysis Effect of Novel Benzofuran–Oxadiazole and Benzofuran–Triazole Hybrids
Novel structural hybrids of benzofuran–oxadiazole and benzofuran–triazole have been synthesized and evaluated for their potential against Staphylococcus aureus, Bacillus subtilis, and Escherichia coli. The excellent antibiotic activity was shown by compou
Faiz, Sadia,Zahoor, Ameer Fawad,Ajmal, Muhammad,Kamal, Shagufta,Ahmad, Sajjad,Abdelgawad, Abdelrahman M.,Elnaggar, Mehrez E.
p. 2839 - 2852
(2019/11/03)

Investigation into improving the aqueous solubility of the thieno[2,3-b]pyridine anti-proliferative agents
It is now established that the thieno[2,3-b]pyridines are a potent class of antiproliferatives. One of the main issues encountered for their clinical application is their low water solubility. In order to improve this, two strategies were pursued. First,
Zafar, Ayesha,Pilkington, Lisa I.,Haverkate, Natalie A.,Van Rensburg, Michelle,Leung, Euphemia,Kumara, Sisira,Denny, William A.,Barker, David,Alsuraifi, Ali,Hoskins, Clare,Reynisson, Jóhannes
(2018/01/18)

Lead Optimization of Benzoxepin-Type Selective Estrogen Receptor (ER) Modulators and Downregulators with Subtype-Specific ERα and ERβ Activity
Estrogen receptor α (ERα) is an important target for the design of drugs such as tamoxifen (2a) and fulvestrant (5). Three series of ER-ligands based on the benzoxepin scaffold structure were synthesized: series I containing an acrylic acid, series II with an acrylamide, and series III with a saturated carboxylic acid substituent. These compounds were shown to be high affinity ligands for the ER with nanomolar IC50 binding values. Series I acrylic acid ligands were generally ERα selective. In particular, compound 13e featuring a phenylpenta-2,4-dienoic acid substituent was shown to be antiproliferative and downregulated ERα and ERβ expression in MCF-7 breast cancer cells. Interestingly, from series III, the phenoxybutyric acid derivative compound 22 was not antiproliferative and selectively downregulated ERβ. A docking study of the benzoxepin ligands was undertaken. Compound 13e is a promising lead for development as a clinically relevant SERD, while compound 22 will be a useful experimental probe for helping to elucidate the role of ERβ in cancer cells.
O'Boyle, Niamh M.,Barrett, Irene,Greene, Lisa M.,Carr, Miriam,Fayne, Darren,Twamley, Brendan,Knox, Andrew J. S.,Keely, Niall O.,Zisterer, Daniela M.,Meegan, Mary J.
p. 514 - 534
(2018/02/07)

S-substituted derivatives of 1,2,4-triazol-3-thiol as new drug candidates for type II diabetes
The therapeutic applications of 1,2,4-triazoles motivated us to synthesize some new derivatives. Two series of S -substituted derivatives (8a–8j, 12a–12i) of 5- (1-[(4-chlorophenyl)sulfonyl]-3-piperidinyl )-4-phenyl-4 H -1,2,4-triazol-3-thiol (6) have been synthesized and evaluated for their biological potential. Using 4-chlorobenzene sulfonyl chloride (1) and ethyl piperidine-3-carboxylate (2), ethyl 1-[(4-chlorophenyl)sulfonyl]piperidine-3-carboxylate (3) was synthesized and converted into 3,4,5-trisubstituted 1,2,4-triazole (6) through formation of the corresponding carbohydrazide (4) and hydrazinecarbothioamide (5). Compound 6 was transformed into 8a–8j by alkyl halides (7a–7j) and into 12a–12i by N -aralkyl/aryl-2-bromoacetamides (11a–11i) in an aprotic solvent. The electrophiles, 11a–11i, were synthesized by gearing up N -substituted aralkyl/aryl amines (10a–10i) with 2-bromoacetyl bromide (9) under dynamic pH control by aqueous sodium carbonate. Structures were elucidated through the spectral techniques of IR, EIMS, 1 H NMR, and 13 C NMR. Most of the synthesized derivatives were found to be potent inhibitors of α -glucosidase enzyme and even better than acarbose. Acarbose is a reference standard and is a commercially available α -glucosidase inhibitor to treat patients with type II diabetes. The low hemolytic activity also emphasized the potential of the synthesized compounds as new drug candidates.
Ur-Rehman, Aziz,Nafeesa, Khadija,Athar Abbasi, Muhammad,Zahra Siddiqui, Sabahat,Rasool, Shahid,Adnan Ali Shah, Syed,Ashraf, Muhammad,Lodhi, Muhammad Arif,Khan, Farman Ali,Jahan, Bakhat
p. 652 - 671
(2018/06/07)

New indole based hybrid oxadiazole scaffolds with N-substituted acetamides: As potent anti-diabetic agents
Current study is based on the sequential conversion of indolyl butanoic acid (1) into ethyl indolyl butanoate (2), indolyl butanohydrazide (3), and 1,3,4-oxadiazole-2-thiol analogs (4) by adopting chemical transformations. In a parallel series of reaction
Nazir, Majid,Abbasi, Muhammad Athar,Aziz-ur-Rehman,Siddiqui, Sabahat Zahra,Khan, Khalid Mohammed,Kanwal,Salar, Uzma,Shahid, Muhammad,Ashraf, Muhammad,Arif Lodhi, Muhammad,Ali Khan, Farman
p. 253 - 263
(2018/09/05)

Synthesis of acetamide derivatives of 1,2,4-triazole bearing azinane and their binding interactions with bovine serum albumin using spectroscopic techniques
A new series of acetamide derivatives containing 1,2,4-triazole and azinane moieties has been synthesized and characterized using1 H NMR,13 C NMR, IR, and EI-MS spectroscopic analysis. The intermediate triazole was synthesized through a sequential synthesis of carboxylate and carbohydrazide. The bovine serum albumin (BSA) binding of the newly synthesized 1,2,4-triazole derivatives was evaluated along with thermodynamics, site-selective binding, and synchronous study. The results obtained by BSA binding as well as thermodynamic studies justify that all the compounds show spontaneous interaction with BSA and could be effectively distributed and eliminated from the body. Therefore, the triazole-based analogs might be a useful strategy for designing new drug systems.
Iqbal, Javed,Ur-Rehman, Aziz,Abbasi, Muhammad Athar,Siddiqui, Sabahat Zahra,Khalid, Hira,Laulloo, Sabina Jhaumeer,Joondan, Nausheen,Taupass, Aniisah Banu,Rasool, Shahid,Shah, Syed Adnan Ali
p. 1459 - 1478
(2019/01/03)

Direct synthesis of N-arylamides via the coupling of aryl diazonium tetrafluoroborates and nitriles under transition-metal-free conditions
The direct synthesis of N-arylamides via the coupling of aryl diazonium tetrafluoroborates and nitriles under transition-metal-free conditions has been developed. The reported protocol is practical and represents an efficient method to produce functionalized amides in moderate to good yields.
Xiong, Biquan,Wang, Gang,Xiong, Tao,Wan, Liming,Zhou, Congshan,Liu, Yu,Zhang, Panliang,Yang, Changan,Tang, Kewen
supporting information
p. 3139 - 3142
(2018/07/13)

A to aryl diazonium tetrafluoroborate salts with a nitrile preparation machine acid radical amine compounds (by machine translation)
The invention provides a high-efficiency, high-selective synthesis of different substituted functional group containing organic amide compound, it adopts the cuprous iodide as a catalyst, in order to aryl diazonium tetrafluoroborate salts compounds and organic nitrile compound as the reaction substrate, the reaction system by adding the organic solvent, water and alkali. The advantage of this method: cheap and easily obtained catalyst; the substrate has a high applicability; mild reaction conditions, safe and reliable; the resulting target product selectivity is close to 100%, yield is as high as 90% or more. The method solves the traditional synthetic organic amide compound of rigorous reaction conditions, the reaction selectivity is poor, the experimental procedure is complicated, the productivity is low and needs to be used for the environment of a harmful reagent and the like, it has good industrial application prospect. The invention also provides a corresponding different substituted functional group containing organic amide compound. (by machine translation)
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Paragraph 0027

(2018/06/04)

Targeting the Hemopexin-like Domain of Latent Matrix Metalloproteinase-9 (proMMP-9) with a Small Molecule Inhibitor Prevents the Formation of Focal Adhesion Junctions
A lack of target specificity has greatly hindered the success of inhibitor development against matrix metalloproteinases (MMPs) for the treatment of various cancers. The MMP catalytic domains are highly conserved, whereas the hemopexin-like domains of MMPs are unique to each family member. The hemopexin-like domain of MMP-9 enhances cancer cell migration through self-interaction and heterointeractions with cell surface proteins including CD44 and α4β1 integrin. These interactions activate EGFR-MAP kinase dependent signaling that leads to cell migration. In this work, we generated a library of compounds, based on hit molecule N-[4-(difluoromethoxy)phenyl]-2-[(4-oxo-6-propyl-1H-pyrimidin-2-yl)sulfanyl]-acetamide, that target the hemopexin-like domain of MMP-9. We identify N-(4-fluorophenyl)-4-(4-oxo-3,4,5,6,7,8-hexahydroquinazolin-2-ylthio)butanamide, 3c, as a potent lead (Kd = 320 nM) that is specific for binding to the proMMP-9 hemopexin-like domain. We demonstrate that 3c disruption of MMP-9 homodimerization prevents association of proMMP-9 with both α4β1 integrin and CD44 and results in the dissociation of EGFR. This disruption results in decreased phosphorylation of Src and its downstream target proteins focal adhesion kinase (FAK) and paxillin (PAX), which are implicated in promoting tumor cell growth, migration, and invasion. Using a chicken chorioallantoic membrane in vivo assay, we demonstrate that 500 nM 3c blocks cancer cell invasion of the basement membrane and reduces angiogenesis. In conclusion, we present a mechanism of action for 3c whereby targeting the hemopexin domain results in decreased cancer cell migration through simultaneous disruption of α4β1 integrin and EGFR signaling pathways, thereby preventing signaling bypass. Targeting through the hemopexin-like domain is a powerful approach to antimetastatic drug development.
Alford, Vincent M.,Kamath, Anushree,Ren, Xiaodong,Kumar, Kunal,Gan, Qianwen,Awwa, Monaf,Tong, Michael,Seeliger, Markus A.,Cao, Jian,Ojima, Iwao,Sampson, Nicole S.
p. 2788 - 2803
(2017/11/27)

A hydroxamic acid derivatives, its pharmaceutical composition, preparation method and use thereof
The invention belongs to the pharmaceutical chemicals field, and relates to a hydroxamic acid derivative, its pharmaceutical composition, a preparation method and an application. The invention relates to a compound shown in a formula I or a formula II, or
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Paragraph 0068-0071

(2017/08/31)

Regioselective synthesis and antimicrobial evaluation of some thioether–amide linked 1,4-disubstituted 1,2,3-triazoles
A series of 1,4-disubstituted 1,2,3-triazoles having thioether as well as amide linkage were synthesized from aryl(prop-2-yn-1-yl)sulfanes and 2-azido-N-substituted acetamides through Cu(I) catalyzed click reaction. Structures of newly synthesized compounds (3a–3x) were confirmed by spectral techniques like FTIR,1H NMR,13C NMR, and HRMS. The synthesized triazoles were evaluated for in vitro antimicrobial activity against Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Staphylococcus aureus, Candida albicans, and Aspergillus niger. Compounds 3m and 3q displayed appreciable broad spectrum antimicrobial activity against tested microbial strains. The nanoformulations of compounds 3m and 3q were also prepared and examined against one bacterial strain and one fungal strain.
Kaushik,Pahwa, Ashima,Thakur, Rajesh,Kaur, Pawan
p. 368 - 378
(2017/02/10)

Synthesis, antimicrobial activity, and QSAR studies of amide-ester linked 1,4-disubstituted 1,2,3-triazoles
Abstract: Synthesis of some amide-ester linked 1,4-disubstituted 1,2,3-triazoles was carried out by employing copper(I)-catalyzed 1,3-dipolar cycloaddition of 2-azido-N-substituted acetamides and benzoic acid prop-2-ynyl esters. All the synthesized 28 1,4-disubstituted 1,2,3-triazoles are new. The synthesized triazoles were characterized by IR, 1H NMR, 13C NMR, HRMS and evaluated for their antimicrobial activity against Staphylococcus aureus, Bacillus subtilis, Escherichia coli, Candida albicans, and Aspergillus niger. Compounds displaying potent antimicrobial activity against each of these microorganisms were found. Quantitative structure activity relationship studies for the synthesized compounds were also carried out to check the effect of various substituents in parent compound on antimicrobial activity. Graphical abstract: [Figure not available: see fulltext.]
Kaushik,Kumar, Krishan,Narasimhan, Balasubramanian,Singh, Dharmendra,Kumar, Pradeep,Pahwa, Ashima
p. 765 - 779
(2017/03/17)

Regioselective synthesis, characterization and antimicrobial evaluation of amide–ether-linked 1,4-disubstituted 1,2,3-triazoles
Regioselective synthesis of some amide–ether-linked 1,4-disubstit-uted 1,2,3-triazoles was realized via the copper(I)-catalyzed click reaction of 1-(prop-2-ynyloxy)naphthalene, 2-(prop-2-ynyloxy)naphthalene and 1,4-bis-(prop-2-ynyloxy)benzene with 2-azido-N-substituted acetamides. The synthesized compounds were characterized by spectral techniques viz. FT-IR,1H--NMR,13C-NMR, HRMS and evaluated for their in vitro antimicrobial activity against Bacillus subtilis, Staphylococcus aureus (Gram-positive bacteria), Pseudomonas aeruginosa, Escherichia coli (Gram-negative bacteria), Candida albicans and Aspergillus brasiliensis (fungi). Among the synthesized 1,4--disubstituted 1,2,3-triazoles, compound 13d displayed excellent antibacterial potential, while, compounds 7d and 13d appeared as potent fungicidal agents against the tested microbial strains. The docking simulation of the broad spectrum microbicidal disubstituted 1,2,3-triazole 13d into the active site of E. coli type II topoisomerase, DNA gyrase B enzyme was also investigated.
Kaushik, Chander Prakash,Kumar, Krishan,Kumar, Devinder,Mor, Satbir,Kumar, Ashwani,Jindal, Deepak Kumar
p. 995 - 1007
(2017/10/13)

2-(Quinolin-4-yloxy)acetamides Are Active against Drug-Susceptible and Drug-Resistant Mycobacterium tuberculosis Strains
2-(Quinolin-4-yloxy)acetamides have been described as potent in vitro inhibitors of Mycobacterium tuberculosis growth. Herein, additional chemical modifications of lead compounds were carried out, yielding highly potent antitubercular agents with minimum inhibitory concentration (MIC) values as low as 0.05 μM. Further, the synthesized compounds were active against drug-resistant strains and were devoid of apparent toxicity to Vero and HaCat cells (IC50s ≥ 20 μM). In addition, the 2-(quinolin-4-yloxy)acetamides showed intracellular activity against the bacilli in infected macrophages with action similar to rifampin, low risk of drug-drug interactions, and no sign of cardiac toxicity in zebrafish (Danio rerio) at 1 and 5 μM. Therefore, these data indicate that this class of compounds may furnish candidates for future development to, hopefully, provide drug alternatives for tuberculosis treatment.
Pissinate, Kenia,Villela, Anne Drumond,Rodrigues, Valnês,Giacobbo, Bruno Couto,Grams, Estêv?o Silveira,Abbadi, Bruno Lopes,Trindade, Rogério Valim,Roesler Nery, Laura,Bonan, Carla Denise,Back, Davi Fernando,Campos, Maria Martha,Basso, Luiz Augusto,Santos, Diógenes Santiago,Machado, Pablo
supporting information
p. 235 - 239
(2016/03/22)

Searching for New Leads for Tuberculosis: Design, Synthesis, and Biological Evaluation of Novel 2-Quinolin-4-yloxyacetamides
In this study, a new series of more than 60 quinoline derivatives has been synthesized and evaluated against Mycobacterium tuberculosis (H37Rv). Apart from the SAR exploration around the initial hits, the optimization process focused on the improvement of the physicochemical properties, cytotoxicity, and metabolic stability of the series. The best compounds obtained exhibited MIC values in the low micromolar range, excellent intracellular antimycobacterial activity, and an improved physicochemical profile without cytotoxic effects. Further investigation revealed that the amide bond was the source for the poor blood stability observed, while some of the compounds exhibited hERG affinity. Compound 83 which contains a benzoxazole ring instead of the amide group was found to be a good alternative, with good blood stability and no hERG affinity, providing new opportunities for the series. Overall, the obtained results suggest that further optimization of solubility and microsomal stability of the series could provide a strong lead for a new anti-TB drug development program.
Pitta, Eleni,Rogacki, Maciej K.,Balabon, Olga,Huss, Sophie,Cunningham, Fraser,Lopez-Roman, Eva Maria,Joossens, Jurgen,Augustyns, Koen,Ballell, Lluis,Bates, Robert H.,Van Der Veken, Pieter
supporting information
p. 6709 - 6728
(2016/08/05)

Design, synthesis and evaluation of novel 19F magnetic resonance sensitive protein tyrosine phosphatase inhibitors
Fluorine is a highly attractive element for both medicinal chemistry and imaging technologies. To facilitate protein tyrosine phosphatase (PTP)-targeted drug discovery and imaging-guided PTP research on fluorine, several highly potent and 19F MR sensitive PTP inhibitors were discovered through a structure-based focused library strategy.
Li, Yu,Xia, Guiquan,Guo, Qi,Wu, Li,Chen, Shizhen,Yang, Zhigang,Wang, Wei,Zhang, Zhong-Yin,Zhou, Xin,Jiang, Zhong-Xing
supporting information
p. 1672 - 1680
(2016/08/24)

Synthesis and cytotoxicity of thieno[2,3-b]quinoline-2-carboxamide and cycloalkyl[b]thieno[3,2-e]pyridine-2-carboxamide derivatives
Seventy nine derivatives of thieno[2,3-b]quinolines, tetrahydrothieno[2,3-b]quinoline, dihydrocyclopenta[b]thieno[3,2-e]pyridine, cyclohepta[b]thieno[3,2-e]pyridine and hexahydrocycloocta[b]thieno[3,2-e]pyridine were either synthesized or obtained commercially and tested for their antiproliferative activity against HCT116, MDA-MB-468 and MDA-MB-231 human cancer cell lines. The most potent eight compounds were active against all cell lines with IC50 values in the 80–250 nM range. In general hexahydrocycloocta[b]thieno[3,2-e]pyridines were most active with increasing activity observed as larger cycloalkyl rings were fused to the pyridine ring.
Leung, Euphemia,Pilkington, Lisa I.,van Rensburg, Michelle,Jeon, Chae Yeon,Song, Mirae,Arabshahi, Homayon J.,De Zoysa, Gayan Heruka,Sarojini, Vijayalekshmi,Denny, William A.,Reynisson, Jóhannes,Barker, David
supporting information
p. 1142 - 1154
(2019/05/24)

2-Oxo-1,2-dihydropyridinyl-3-yl amide-based GPa inhibitors: Design, synthesis and structure-activity relationship study
Glycogen phosphorylase (GP), which plays a crucial role in the conversion of glycogen to glucose-1-phosphate, is a target for therapeutic intervention in diabetes. In this study, we report the design and synthesis of 29 new derivatives of 2-oxo-1,2-dihydro pyridin-3-yl amides, as potential inhibitors of GP. The hit rate (45%) was high with 13 compounds inhibiting GPa (between 33% at 4.40 mM and an IC50 of 1.92 μM). Two lead compounds were identified as compounds exhibiting good GPa inhibition (IC50 = 2.1 and 1.92 μM). SAR analysis of these compounds revealed sensitivity of GPa to the length of the 2-oxo-1,2-dihydro pyridin-3-yl amide derivative and a preference for inclusion of a 3,4-dichlorobenzyl moiety.
Loughlin, Wendy A.,Jenkins, Ian D.,Karis, N. David,Schweiker, Stephanie S.,Healy, Peter C.
supporting information
p. 1 - 14
(2016/02/18)