Design and synthesis of screening libraries based on the muurolane natural product scaffold

被引：32

作者：

Barnes, Emma C. ^{[1
]}

Choomuenwai, Vanida ^{[1
]}

Andrews, Katherine T. ^{[1
,2
]}

Quinn, Ronald J. ^{[1
]}

Davis, Rohan A. ^{[1
]}

机构：

[1] Griffith Univ, Eskitis Inst, Nathan, Qld 4111, Australia

[2] Queensland Inst Med Res, Herston, Qld 4006, Australia

来源：

ORGANIC & BIOMOLECULAR CHEMISTRY | 2012年 / 10卷 / 20期

基金：

澳大利亚研究理事会;

关键词：

SOLID-PHASE SYNTHESIS; DRUG DISCOVERY; COMBINATORIAL CHEMISTRY; CHEMICAL SPACE; LEADS; SESQUITERPENES; DERIVATIVES; EREMOPHILA; DIVERSITY; ALCOHOLS;

D O I：

10.1039/c2ob00029f

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

The plant-derived natural product 14-hydroxy-6,12-muuroloadien-15-oic acid (1) was identified as a unique scaffold that could be chemically elaborated to generate novel lead-or drug-like screening libraries. Prior to synthesis a virtual library was generated and prioritised based on drug-like physicochemical parameters such as log P, log D-5.5, hydrogen bond donors/acceptors, and molecular weight. The natural product scaffold (1) was isolated from the endemic Australian plant Eremophila mitchellii and then utilised in the parallel solution-phase generation of two series of analogues. The first library consisted of six semi-synthetic amide derivatives, whilst the second contained six carbamate analogues. These libraries have been evaluated for antimalarial activity using a chloroquine-sensitive Plasmodium falciparum line (3D7) and several compounds displayed low to moderate activity with IC50 values ranging from 14 to 33 mu M.

引用

页码：4015 / 4023

页数：9

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