New quinoxalin‐1,3,4‐oxadiazole derivatives: Synthesis, characterization, in vitro biological evaluations, and molecular modeling studies

• Published in: Archiv der Pharmazie (Weinheim) Vol. 354; no. 9; pp. e2000471 - n/a
• Main Authors: Mirzazadeh, Roghieh, Asgari, Mohammad S., Barzegari, Ebrahim, Pedrood, Keyvan, Mohammadi‐Khanaposhtani, Maryam, Sherafati, Maedeh, Larijani, Bagher, Rastegar, Hossein, Rahmani, Hojjat, Mahdavi, Mohammad, Taslimi, Parham, Üç, Eda M., Gulçin, İlhami
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 01.09.2021; Wiley Subscription Services, Inc
• Subjects: 1,3,4‐oxadiazole; carbonic anhydrase; Carbonic Anhydrase Inhibitors - chemical synthesis; Carbonic Anhydrase Inhibitors - chemistry; Carbonic Anhydrase Inhibitors - pharmacology; Chemistry; Chemistry, Medicinal; Chemistry, Multidisciplinary; cholinesterase; Cholinesterase Inhibitors - chemical synthesis; Cholinesterase Inhibitors - chemistry; Cholinesterase Inhibitors - pharmacology; Enzymes; Glycoside Hydrolase Inhibitors - chemical synthesis; Glycoside Hydrolase Inhibitors - chemistry; Glycoside Hydrolase Inhibitors - pharmacology; Humans; Life Sciences & Biomedicine; Models, Molecular; Molecular Docking Simulation; Oxadiazoles - chemical synthesis; Oxadiazoles - chemistry; Oxadiazoles - pharmacology; Pharmacology & Pharmacy; Physical Sciences; quinoxalin; Quinoxalines - chemical synthesis; Quinoxalines - chemistry; Quinoxalines - pharmacology; Science & Technology; Structure-Activity Relationship; α‐glucosidase; alpha-glucosidase; CARBONIC-ANHYDRASE; cholinesterase; 1,3,4-oxadiazole; CRYSTAL-STRUCTURE; carbonic anhydrase; INHIBITORY PROPERTIES; AGENTS; SALTS; quinoxalin; α-glucosidase
• ISSN: 0365-6233; 1521-4184
• DOI: 10.1002/ardp.202000471

A new series of quinoxalin‐1,3,4‐oxadiazole (10a–l) derivatives was synthesized and evaluated against some metabolic enzymes including human carbonic anhydrase (hCA) isoenzymes I and II (carbonic anhydrases I and II), cholinesterase (acetylcholinesterase and butyrylcholinesterase), and α‐glucosidase. Obtained data revealed that all the synthesized compounds were more potent as compared with the used standard inhibitors against studied target enzymes. Among the synthesized compounds, 4‐fluoro derivative (10f) against hCA I, 4‐chloro derivative (10i) against hCA II, 3‐fluoro derivative (10e) against acetylcholinesterase and butyrylcholinesterase, and 3‐bromo derivative (10k) against α‐glucosidase were the most potent compounds with inhibitory activity around 1.8‐ to 7.37‐fold better than standard inhibitors. Furthermore, docking studies of these compounds were performed at the active site of their target enzymes. A new series of quinoxalin‐1,3,4‐oxadiazole (10a–l) derivatives was synthesized and evaluated against human carbonic anhydrase isoenzymes I and II, acetylcholinesterase, butyrylcholinesterase, and α‐glucosidase. All the synthesized compounds were more potent than the used standard inhibitors against the studied target enzymes. Docking studies of these compounds at the active sites of their target enzymes were performed.