Synthesis, antimalarial activity and cytotoxicity of 10-aminoethylether derivatives of artemisinin

被引：14

作者：

Cloete, Theunis T. ^{[1
]}

Breytenbach, J. Wilma ^{[2
]}

de Kock, Carmen ^{[3
]}

Smith, Peter J. ^{[3
]}

Breytenbach, Jaco C. ^{[1
]}

N'Da, David D. ^{[1
]}

机构：

[1] North West Univ, Dept Pharmaceut Chem, ZA-2520 Potchefstroom, South Africa

[2] North West Univ, Stat Consultat Serv, ZA-2520 Potchefstroom, South Africa

[3] Univ Cape Town, Dept Pharmacol, Groote Schuur Hosp, ZA-7925 Observatory, South Africa

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2012年 / 20卷 / 15期

基金：

新加坡国家研究基金会;

关键词：

Artemisinin; Plasmodium falciparum; Microwave; Malaria; ASSAY; MECHANISMS;

D O I：

10.1016/j.bmc.2012.06.014

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：

In this study, a series of 11 10-aminoethylether derivatives of artemisinin were synthesised and their antimalarial activity against both the chloroquine sensitive (D10) and resistant (Dd2) strains of Plasmodium falciparum was determined. The compounds were prepared by introducing aliphatic, alicyclic and aromatic amine groups with linkers of various chain lengths through an ethyl ether bridge at C-10 of artemisinin using conventional and microwave assisted syntheses, and their structures were confirmed by NMR and HRMS. All derivatives proved to be active against both strains of the parasite. The highest overall activity was displayed by the short chain aromatic derivative 8 (IC50 = 1.44 nM), containing only one nitrogen atom, while long chain polyamine derivatives were found to have the lowest activity against both strains. An interesting correlation between the IC50, pK(a) values and resistance index (RI) was found. (C) 2012 Elsevier Ltd. All rights reserved.

引用

页码：4701 / 4709

页数：9

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