Synthesis of 6-hydroxyaurone analogues and evaluation of their α-glucosidase inhibitory and glucose consumption-promoting activity: Development of highly active 5, 6-disubstituted derivatives. Issue 15 (1st August 2017)

• Record Type: Journal Article
• Authors: Sun, Hua; Ding, Weina; Song, Xiaotong; Wang, Dong; Chen, Mingzhu; Wang, Kaili; Zhang, Yazhou; Yuan, Peng; Ma, Ying; Wang, Runling; Dodd, Robert H.; Zhang, Yongmin; Lu, Kui; Yu, Peng
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 27:Issue 15(2017)
• Page Start: 3226
• Page End: 3230
• Publication Date: 2017-08-01
• Subjects: Aurone -- α-Glucosidase inhibitor -- Inhibitory mechanism -- Docking analysis -- Glucose consumption; FSTRHKHJVFRMTO-SXGWCWSVSA-N -- GHQUBVFRAYRSQR-SXGWCWSVSA-N -- VXSRECFQBNMFIH-JMIUGGIZSA-N -- KDGIFQNPGMXJCY-ZSOIEALJSA-N -- WEEYRFRNWMFAKW-AUWJEWJLSA-N -- ZVSCXJXQVYHWIJ-AUWJEWJLSA-N -- KEZLDSPIRVZOKZ-AUWJEWJLSA-N -- BUKHGPNESZFJDD-UKWGHVSLSA-N -- YUCCNWHJQXNUQE-PXNMLYILSA-N -- MKRZQRDYRUVFAW-RZNTYIFUSA-N -- RGNXWPVNPFAADO-NSIKDUERSA-N -- XRGFWIGELKXXDX-UHFFFAOYSA-N -- KTQJHWMANKCAJA-UHFFFAOYSA-N -- BLLMRPOVMOPQKC-UHFFFAOYSA-N -- FLMGERIKVIKEQL-UHFFFAOYSA-N -- FBPIJKXDGIROJA-UHFFFAOYSA-N -- QQFVYNIZQBXIJP-UHFFFAOYSA-N -- KXRXGFUGGMYLIZ-UHFFFAOYSA-N -- CJHRHUVBYQCKLL-UHFFFAOYSA-N -- VBLUTCMVJFVVJW-UHFFFAOYSA-N -- ZTILJZVSCFLLLC-UHFFFAOYSA-N -- XPZXYVIDVPTQJO-UHFFFAOYSA-N -- NNFLRNVPHGPHIX-MTJSOVHGSA-N -- RDTPQSDGDHJUCN-NHDPSOOVSA-N -- GRCCGQBWKWMNHO-YVLHZVERSA-N -- YDZUCHRNTYXYQU-XKZIYDEJSA-N -- IYQPBUNMVBOGID-WQRHYEAKSA-N; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2017.06.040
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: A series of 6-hydroxyaurones and their analogues have been synthesized and evaluated for their in vitro α-glucosidase inhibitory and glucose consumption-promoting activity. These compounds exhibited varying degrees of α-glucosidase inhibitory activity, 11 of them showing higher potency than that of the control standard acarbose (IC50 = 50.30 μM). Surprisingly, analogues devoid of a substituent at C-2 but having an aryl group at C-5 were found to be highly active (e.g., 7f, IC50 = 9.88 μM). Docking analysis substantiated these findings. The kinetic analysis of compound7f, the most potent α-glucosidase inhibitor of this study, revealed that it inhibited α-glucosidase in an irreversible and mixed competitive mode. In addition, compounds7f and10c exhibited significant glucose consumption promoting activity at 1 μM.