Synthesis and biological characterisation of ester and amide derivatives of fusidic acid as antiplasmodial agents

被引：24

作者：

Espinoza-Moraga, Marlene ^{[1
]}

Singh, Kawaljit ^{[1
]}

Njoroge, Mathew ^{[1
]}

Kaur, Gurminder ^{[1
]}

Okombo, John ^{[1
]}

De Kock, Carmen ^{[3
]}

Smith, Peter J. ^{[3
]}

Wittlin, Sergio ^{[4
,5
]}

Chibale, Kelly ^{[1
,2
,6
]}

机构：

[1] Univ Cape Town, Dept Chem, ZA-7701 Rondebosch, South Africa

[2] Univ Cape Town, South African Med Res Council, Drug Discovery & Dev Res Unit, ZA-7701 Rondebosch, South Africa

[3] Univ Cape Town, Groote Schuur Hosp, Fac Hlth Sci, Div Clin Pharmacol,OMB, K45, ZA-7925 Observatory, South Africa

[4] Swiss Trop & Publ Hlth Inst, Socinstr 57, CH-4002 Basel, Switzerland

[5] Univ Basel, CH-4002 Basel, Switzerland

[6] Univ Cape Town, Inst Infect Dis & Mol Med, ZA-7701 Rondebosch, South Africa

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2017年 / 27卷 / 03期

基金：

英国医学研究理事会;

关键词：

Fusidic acid; Malaria; Antiplasmodial; ELONGATION-FACTOR-G; NATURAL-PRODUCTS; ANTIMALARIAL; SENSITIVITY; RESISTANCE; MALARIA;

D O I：

10.1016/j.bmcl.2016.11.077

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of novel fusidic acid (FA) derivatives was synthesized by replacing the carboxylic acid group with various ester and amide groups and evaluated in vitro for their antiplasmodial activity against the chloroquine-sensitive NF54 and multidrug-resistant K1 strains of the malarial parasite Plasmodium falciparum. Most of these derivatives showed a 4-49 and 5-17-fold increase in activity against NF54 and RI strains, respectively, as compared to FA and had a good selectivity index. These derivatives are stable over the incubation period and do not appear to be prodrugs of fusidic acid. (C) 2016 Elsevier Ltd. All rights reserved.

引用

页码：658 / 661

页数：4

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