Varic acid analogues from fungus as PTP1B inhibitors: Biological evaluation and structure-activity relationships

被引：14

作者：

Sun, Wenlong ^{[1
]}

Zhuang, Chunlin ^{[4
]}

Li, Xia ^{[1
]}

Zhang, Bowei ^{[1
]}

Lu, Xinhua ^{[2
,3
]}

Zheng, Zhihui ^{[2
,3
]}

Dong, Yuesheng ^{[1
]}

机构：

[1] Dalian Univ Technol, Sch Life Sci, Biotechnol, Dalian 116024, Liaoning, Peoples R China

[2] North China Pharmaceut Grp Corp, New Drug Res & Dev Ctr, Shijiazhuang 050015, Hebei, Peoples R China

[3] Natl Microbial Med Engn & Res Ctr, Shijiazhuang 050015, Hebei, Peoples R China

[4] Second Mil Med Univ, Sch Pharm, 325 Guohe Rd, Shanghai 200433, Peoples R China

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2017年 / 27卷 / 15期

基金：

中国国家自然科学基金;

关键词：

PTP1B; Varic acid; Structure-activity relationships; Insulin-sensitizing effect; Type 2 diabetes mellitus; PHOSPHATASE 1B PTP1B; INSULIN SENSITIVITY; TRIVARIC ACID; MICE;

D O I：

10.1016/j.bmcl.2017.06.001

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Protein tyrosine phosphatase 1B ( PTP1B) inhibitors as potential therapies for diabetes and obesity have attracted much attention in recent years. Six varic acid analogues were isolated from two strains of fungi and evaluated for PTP1B inhibition activities. The structure-activity relationships were also characterized and predicted by molecular modeling. Further kinetic studies indicated the reversible and competitive inhibition manner of varic acid analogues. Trivaric acid showed insulin-sensitizing effect not only in vitro but also in vivo, representing a promising lead compound for further optimization. (C) 2017 Elsevier Ltd. All rights reserved.

引用

页码：3382 / 3385

页数：4

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