Design and synthesis of natural product derivatives with selective and improved cytotoxicity based on a sesquiterpene scaffold

被引：9

作者：

Zhang, Yang ^{[1
]}

Zhang, Zhuowei ^{[1
]}

Wang, Bo ^{[1
]}

Liu, Ling ^{[2
]}

Che, Yongsheng ^{[1
]}

机构：

[1] Beijing Inst Pharmacol & Toxicol, State Key Lab Toxicol & Med Countermeasures, Beijing 100850, Peoples R China

[2] Chinese Acad Sci, Inst Microbiol, State Key Lab Mycol, Beijing 100101, Peoples R China

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2016年 / 26卷 / 08期

基金：

中国国家自然科学基金;

关键词：

Brasilamide E; Synthesis; Derivatives; Selectivity; Cytotoxicity; BISABOLANE SESQUITERPENOIDS; APOPTOSIS; INHIBITORS; POTENT; POLYPHENOLS; TERPENOIDS; CELLS;

D O I：

10.1016/j.bmcl.2016.03.022

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Brasilamide E (1) is a bisabolane sesquiterpenoid isolated from the solid-substrate fermentation cultures of a plant endophytic fungus Paraconiothyrium brasiliense. The compound specifically inhibited proliferation of the MCF-7 cells, but did not show cytotoxicity towards the negative controls HaCaT and NIH3T3 cells (IC50 > 50 mu M). To improve its potency while maintain selectivity, a total of 27 derivatives of 1 were designed, synthesized, and evaluated for in vitro cytotoxicity against six tumor cell lines and the negative control NIH3T3 cells. Among these compounds, compound 12b showed significantly improved potency against the MCF-7, HeLa, and HO8910 cells with IC50 values of 0.13-0.25 mu M compared to 1 (IC50 8.47-18.00 mu M), and remained nontoxic to the NIH3T3 cells. (C) 2016 Elsevier Ltd. All rights reserved.

引用

页码：1885 / 1888

页数：4

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