349120-89-4Relevant articles and documents
Probing phenylcarbamoylazinane-1,2,4-triazole amides derivatives as lipoxygenase inhibitors along with cytotoxic, ADME and molecular docking studies
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)
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.
A novel method for the synthesis of 1,2,4-triazole-derived heterocyclic compounds: enzyme inhibition and molecular docking studies
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)
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.
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
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)
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.
