Synthesis of novel flavonoid alkaloids as α-glucosidase inhibitors

被引：58

作者：

Zhen, Jing ^{[1
,2
]}

Dai, Yujie ^{[3
]}

Villani, Tom ^{[1
,2
]}

Giurleo, Daniel ^{[1
,2
]}

Simon, James E. ^{[1
,2
]}

Wu, Qingli ^{[1
,2
]}

机构：

[1] Rutgers State Univ, Dept Plant Biol, New Use Agr & Nat Plant Prod Program, 59 Dudley Rd, New Brunswick, NJ 08901 USA

[2] Rutgers State Univ, Ernest Mario Sch Pharm, Dept Med Chem, 160 Frelinghuysen Rd, Piscataway, NJ 08854 USA

[3] Tianjin Univ Sci & Technol, Key Lab Ind Fermentat Microbiol, Tianjin 300457, Peoples R China

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2017年 / 25卷 / 20期

关键词：

Flavonoid alkaloid; Flavonoid; alpha-Glucosidase inhibitor; Diabetes; Molecular docking study; SAR; DOCKING;

D O I：

10.1016/j.bmc.2017.07.055

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

A series of novel flavonoid alkaloids were synthesized with different flavonoids and attached nitrogen-containing moieties. These new compounds were screened for inhibitory activity of alpha-glucosidase, among which compound 23 was found to show the lowest IC50 of 4.13 mu M. Kinetic analysis indicates that the synthesized compounds 15 and 23 inhibit the enzyme in a non-competitive model with Ki value of 37.8 +/- 0.8 mu M and 13.2 +/- 0.6 mu M. Further docking studies suggest that the preferred binding pocket is close to the catalytic center, correlating to the experimental results. Structure activity relationship studies (SAR) indicate that 4'-hyroxyl group and the 4-position carbonyl group in the flavonoid structure are important for this biological activity. Addition of extra hydrogen bonding and hydrophobic groups on ring A would increase the inhibitory activity. (C) 2017 Elsevier Ltd. All rights reserved.

引用

页码：5355 / 5364

页数：10

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