New transition metal complexes containing imidazole rings endowed with potential antiamoebic activity

被引：8

作者：

Wani, Mohmmad Younus ^{[1
,4
]}

Bhat, Abdul Roouf ^{[2
]}

Azam, Amir ^{[3
]}

Athar, Fareeda ^{[1
]}

Sobral, Abilio J. F. N. ^{[4
]}

机构：

[1] Jamia Millia Islamia, Ctr Interdisciplinary Res Basic Sci, New Delhi 110025, India

[2] SP Coll, Dept Chem, MA Rd, Srinagar 190001, Jammu & Kashmir, India

[3] Jamia Millia Islamia, Dept Chem, New Delhi 110025, India

[4] Univ Coimbra, FCTUC, Dept Quim, Rua Larga, P-3004535 Coimbra, Portugal

来源：

MEDCHEMCOMM | 2016年 / 7卷 / 05期

关键词：

ENTAMOEBA-HISTOLYTICA; IN-VITRO; COPPER(II) COMPLEXES; THIOREDOXIN; LIGAND; EPR; CYTOTOXICITY; TETRAZOLE; DOCKING; GROWTH;

D O I：

10.1039/c6md00013d

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 useful concept for the rational design of anti-protozoal drug candidates is the complexation of bioactive ligands with transition metals. We previously reported that nitroimidazole acylhydrazones possess excellent antiamoebic activity; in this study, we synthesized some Cu-II, Co-II and Ni-II metal complexes and chose 2-(5-methyl-2-nitro-1H-imidazol-1-yl)-N'-[(E)-pyridin-2-ylmethylidene]acetohydrazide as a ligand. Physical and spectroscopic characterization revealed a distorted octahedral geometry for the complexes. The pharmacological characterization, including assays against Entamoeba histolytica and cytotoxicity to mammalian cells, revealed that chelation improves the antiamoebic activity of the ligand. Docking of the ligand with thioredoxin reductase (EhTrR), a promising target for the treatment of amoebiasis, showed that the inhibitor snugly fits the active site of the target enzyme, which may well explain the excellent inhibitory activity.

引用

页码：982 / 989

页数：8

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