α‐Glucosidase Inhibition by Usnic Acid Derivatives

• Published in: Chemistry & biodiversity Vol. 18; no. 4; pp. e2000906 - n/a
• Main Authors: Nguyen, Huy Truong, Devi, Asshaima Paramita, Nguyen, Tran‐Van‐Anh, Chavasiri, Warinthorn, Pham, Duc‐Dung, Sichaem, Jirapast, Nguyen, Ngoc‐Hong, Huynh, Bui‐Linh‐Chi, Nguyen, Van‐Kieu, Duong, Thuc Huy
• Format: Journal Article
• Language: English
• Published: Switzerland Wiley Subscription Services, Inc 01.04.2021
• Subjects: Acarbose; Analogs; Benzofuran; benzylidene derivative; Dakin oxidation; Enzyme inhibitors; Enzymes; Glucosidase; Synthesis; Usnic acid; α-glucosidase inhibition; α-glucosidase inhibition; Dakin oxidation; benzylidene derivative; usnic acid
• ISSN: 1612-1872; 1612-1880
• DOI: 10.1002/cbdv.202000906

This study investigated a set of new potential antidiabetes agents. Derivatives of usnic acid were designed and synthesized. These analogs and nineteen benzylidene analogs from a previous study were evaluated for enzyme inhibition of α‐glucosidase. Analogs synthesized using the Dakin oxidative method displayed stronger activity than the pristine usnic acid (IC50>200 μM). Methyl (2E,3R)‐7‐acetyl‐4,6‐dihydroxy‐2‐(2‐methoxy‐2‐oxoethylidene)‐3,5‐dimethyl‐2,3‐dihydro‐1‐benzofuran‐3‐carboxylate (6b) and 1,1′‐(2,4,6‐trihydroxy‐5‐methyl‐1,3‐phenylene)di(ethan‐1‐one) (6e) were more potent than an acarbose positive control (IC50 93.6±0.49 μM), with IC50 values of 42.6±1.30 and 90.8±0.32 μM, respectively. Most of the compounds synthesized from the benzylidene series displayed promising activity. (9bR)‐2,6‐Bis[(2E)‐3‐(2‐chlorophenyl)prop‐2‐enoyl]‐3,7,9‐trihydroxy‐8,9b‐dimethyldibenzo[b,d]furan‐1(9bH)‐one (1c), (9bR)‐3,7,9‐trihydroxy‐8,9b‐dimethyl‐2,6‐bis[(2E)‐3‐phenylprop‐2‐enoyl]dibenzo[b,d]furan‐1(9bH)‐one (1g), (9bR)‐2‐acetyl‐6‐[(2E)‐3‐(2‐chlorophenyl)prop‐2‐enoyl]‐3,7,9‐trihydroxy‐8,9b‐dimethyldibenzo[b,d]furan‐1(9bH)‐one (2d), (9bR)‐2‐acetyl‐6‐[(2E)‐3‐(3‐chlorophenyl)prop‐2‐enoyl]‐3,7,9‐trihydroxy‐8,9b‐dimethyldibenzo[b,d]furan‐1(9bH)‐one (2e), (6bR)‐8‐acetyl‐3‐(4‐chlorophenyl)‐6,9‐dihydroxy‐5,6b‐dimethyl‐2,3‐dihydro‐1H‐[1]benzofuro[2,3‐f][1]benzopyran‐1,7(6bH)‐dione (3e), (6bR)‐8‐acetyl‐6,9‐dihydroxy‐5,6b‐dimethyl‐3‐phenyl‐2,3‐dihydro‐1H‐[1]benzofuro[2,3‐f][1]benzopyran‐1,7(6bH)‐dione (3h), (6bR)‐3‐(2‐chlorophenyl)‐8‐[(2E)‐3‐(2‐chlorophenyl)prop‐2‐enoyl]‐6,9‐dihydroxy‐5,6b‐dimethyl‐2,3‐dihydro‐1H‐[1]benzofuro[2,3‐f][1]benzopyran‐1,7(6bH)‐dione (4b), and (9bR)‐6‐acetyl‐3,7,9‐trihydroxy‐8,9b‐dimethyl‐2‐[(2E)‐3‐phenylprop‐2‐enoyl]dibenzo[b,d]furan‐1(9bH)‐one (5c) were the most potent α‐glucosidase enzyme inhibitors, with IC50 values of 7.0±0.24, 15.5±0.49, 7.5±0.92, 10.9±0.56, 1.5±0.62, 15.3±0.54, 19.0±1.00, and 12.3±0.53 μM, respectively.