Lowering of 5-nitroimidazole's mutagenicity: Towards optimal antiparasitic pharmacophore

被引：50

作者：

Crozet, Maxime D. ^{[1
]}

Botta, Celine ^{[3
]}

Gasquet, Monique ^{[2
]}

Curti, Christophe ^{[1
]}

Remusat, Vincent ^{[1
]}

Hutter, Sebastien ^{[2
]}

Chapelle, Olivier ^{[2
]}

Azas, Nadine ^{[2
]}

De Meo, Michel ^{[3
]}

Vanelle, Patrice ^{[1
]}

机构：

[1] Univ Aix Marseille I II & III, Fac Pharm, Lab Pharmacochim Radicalaire, CNRS,UMR 6264,Lab Chim Provence, F-13385 Marseille 05, France

[2] Univ Mediterranee, Fac Pharm, Lab Biogenotoxicol & Mutagenese Environm, EA 1784,IFR PMSE 112, F-13385 Marseille 05, France

[3] Univ Mediterranee, Fac Pharm, UMR MD3, Lab Parasitol Mycol Med Hyg & Zool, F-13385 Marseille 05, France

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2009年 / 44卷 / 02期

关键词：

5-Nitroimidazoles; Arylsulfonylmethyl group; Antiparasitic activity; Mutagenicity; VICARIOUS NUCLEOPHILIC-SUBSTITUTION; ORGANIC-ANIONS; METRONIDAZOLE; TRICHOMONAS; DERIVATIVES; DRUGS; GENOTOXICITY; HYDROGEN; STRAINS; GIARDIA;

D O I：

10.1016/j.ejmech.2008.05.015

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

To improve the antiparasitic pharmacophore, 20 5-nitroimidazoles bearing an arylsulfonylmethyl group were prepared from commercial imidazoles. The antiparasitic activity of these molecules was assessed against Trichomonas vaginalis, the in vitro cytotoxicity was evaluated on human monocytes and the mutagenicity was determined by the Salmonella mutagenicity assay. All IC50 on T. vaginalis were below the one of metronidazole. The determination of the specificity indexes (SIs), defined as the ratios of the cytotoxic activity and the antitrichomonas activity, indicated that 11 derivatives had a SI over the one of metronidazole. Molecules, bearing an additional methyl group on the 2-position, showed a lower mutagenicity than metronidazole. Moreover, three derivatives were characterized by a low mutagenicity and an efficient antitrichomonas activity. (C) 2008 Elsevier Masson SAS. All rights reserved.

引用

页码：653 / 659

页数：7

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