Antiplasmodial activities of gold(I) complexes involving functionalized N-heterocyclic carbenes

被引：20

作者：

Hemmert, Catherine ^{[1
,2
]}

Ramadani, Arba Pramundita ^{[1
,2
,3
]}

Boselli, Luca ^{[1
,2
]}

Alvarez, Alvaro Fernandez ^{[1
,2
]}

Paloque, Lucie ^{[1
,2
]}

Augereau, Jean-Michel ^{[1
,2
]}

Gornitzka, Heinz ^{[1
,2
]}

Benoit-Vical, Franoise ^{[1
,2
]}

机构：

[1] CNRS, LCC, 205 Route Narbonne,BP 44099, F-31077 Toulouse 4, France

[2] Univ Toulouse, UPS, INPT, F-31077 Toulouse 4, France

[3] Univ Gadjah Mada, Fac Med, Yogyakarta, Indonesia

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2016年 / 24卷 / 13期

关键词：

N-Heterocyclic carbene; Gold; Organometallic complexes; Antiplasmodial drugs; METAL-BASED CHEMOTHERAPY; ACTIVITY IN-VITRO; ANTIMALARIAL ACTIVITY; TROPICAL DISEASES; VIVO; INHIBITION; FERROQUINE; AGENTS;

D O I：

10.1016/j.bmc.2016.05.023

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：

A series of twenty five molecules, including imidazolium salts functionalized by N-, O- or S-containing groups and their corresponding cationic, neutral or anionic gold(I) complexes were evaluated on Plasmodium falciparum in vitro and then on Vero cells to determine their selectivity. Among them, eight new compounds were synthesized and fully characterized by spectroscopic methods. The X-ray structures of three gold(I) complexes are presented. Except one complex (18), all the cationic gold(I) complexes show potent antiplasmodial activity with IC50 in the micro-and submicromolar range, correlated with their lipophilicity. Structure-activity relationships enable to evidence a lead-complex (21) displaying a good activity (IC50 = 210 nM) close to the value obtained with chloroquine (IC50 = 514 nM) and a weak cytotoxicity. (C) 2016 Elsevier Ltd. All rights reserved.

引用

页码：3075 / 3082

页数：8

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