Synthesis and structure elucidation of a cobalt(II) complex as topoisomerase I inhibitor: In vitro DNA binding, nuclease and RBC hemolysis

被引：35

作者：

Ahmad, Musheer ^{[1
]}

Afzal, Mohd ^{[2
]}

Tabassum, Sartaj ^{[2
]}

Kalniska, Bozena ^{[3
]}

Mrozinski, Jerzy ^{[3
]}

Bharadwaj, Parimal K. ^{[1
]}

机构：

[1] Indian Inst Technol, Dept Chem, Kanpur 208016, UP, India

[2] Aligarh Muslim Univ, Dept Chem, Aligarh 202002, UP, India

[3] Univ Wroclaw, Fac Chem, PL-50383 Wroclaw, Poland

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2014年 / 74卷

关键词：

CT DNA binding; pBR322 DNA cleavage; T4 DNA ligase assay; Topo I inhibition activity; Molecular docking; LIGAND COPPER(II) COMPLEXES; METAL-COMPLEXES; MAGNETIC-PROPERTIES; CLEAVAGE ACTIVITY; TRANSITION-METAL; ACID; CHEMISTRY; CAMPTOTHECIN; DESIGN; DOCKING;

D O I：

10.1016/j.ejmech.2013.10.025

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Metal-based cancer chemotherapeutic agent of the type Co(II) complex [Co(mpca)(2)].H(2)0 (1), where, Hmpca = 9-methyl-[1,10] phenanthroline-2-carboxylic acid was synthesized and characterized by various spectroscopic and analytical techniques and further authenticated by single crystal X-ray diffraction methods. In vitro DNA binding studies of complex 1 with CT DNA was carried out by several biophysical techniques in accordance with molecular docking technique which revealed that 1 binds to DNA via intercalation mode having GC-rich sequences. Complex 1 cleaves pBR322 DNA via hydrolytic pathway (validated by T4 DNA ligase assay). Furthermore, complex 1 exhibits significant inhibitory effects on the catalytic activity of Topo-I at 25 mu m concentration and further validated by molecular docking studies. (C) 2013 Elsevier Masson SAS. All rights reserved.

引用

页码：683 / 693

页数：11

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