α-Glucosidase inhibition activity and in silico study of 2-(benzo[d][1,3]dioxol-5-yl)-4H-chromen-4-one, a synthetic derivative of flavone

A synthetic flavone derivative 2-(benzo[d][1,3]dioxol-5-yl)-4H-chromen-4-one (BDC) was synthesized by the one pot reaction method and assessed for α-glucosidase inhibitory activity. The BDC demonstrated dose dependent inhibition of α-glucosidase activity. A maximum inhibition (99.3 ± 0.26%) of α-glucosidase was observed at 27.6 µM. The maximum α-glucosidase inhibitory activity depicted by BDC 27.6 µM concentration was 22.4 fold over the maximum inhibition observed with acarbose (97.72 ± 0.59% at 669.57 µM), a standard commercial anti-diabetic drug. In contrast to acarbose that depicted competitive type inhibition, kinetic studies of α-glucosidase inhibition by BDC demonstrated non-competitive inhibition with Km of 0.71 mM−1 and a Vmax of 0.028 mmol/min. In silico studies suggest allosteric interaction of BDC with α-glucosidase at a minimum binding energy (ΔG) of −8.64 kcal/mol and Ki of 465.3 nM, whereas, acarbose interacted at the active site of α-glucosidase with ΔG of −9.23 kcal/mol and Ki of 172 nM. Thus BDC significantly inhibited α-glucosidase in comparison to acarbose. Moreover, BDC has been endorsed for drug likeness by evaluating it as per Lipinski rule of five. Thus, BDC can be a lead compound for the management of type-2 diabetes mellitus. © 2018 Elsevier Ltd

Авторы
Meena S.N.1 , Kumar U.1 , Naik M.M.2 , Ghadi S.C.1 , Tilve S.G. 2, 3
Язык
Английский
Статус
Опубликовано
Год
2018
Организации
  • 1 Department of Biotechnology, Goa University, Taleigao Plateau, Goa 403 206, India
  • 2 Department of Chemistry, Goa University, Taleigao Plateau, Goa 403 206, India
  • 3 Organic Chemistry Department, RUDN University, 6 Miklukho-Maklay Street, Moscow, 117198, Russian Federation
Ключевые слова
2-(Benzo[d][1,3]dioxol-5-yl)-4H-chromen-4-one (BDC); Acarbose; Anti-diabetic compounds; Non-competitive; α-Glucosidase
Дата создания
04.02.2019
Дата изменения
04.02.2019
Постоянная ссылка
https://repository.rudn.ru/ru/records/article/record/36418/