Molecular drug design, synthesis and crystal structure determination of CuII-SnIV heterobimetallic core: DNA binding and cleavage studies

被引：78

作者：

Arjmand, Farukh ^{[1
]}

Parveen, Shazia ^{[1
]}

Afzal, Mohd ^{[1
]}

Toupet, Loic ^{[2
]}

Ben Hadda, Taibi ^{[3
]}

机构：

[1] Aligarh Muslim Univ, Dept Chem, Aligarh 202002, Uttar Pradesh, India

[2] Univ Rennes 1, Inst Phys Rennes, UMR 625, F-35042 Rennes, France

[3] Univ Mohammed 1, Lab Chim Mat, FSO, Oujda 60000, Morocco

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2012年 / 49卷

关键词：

Cu-II-Sn-IV phen complex; CT DNA binding; pBR322 DNA cleavage; 14 DNA ligase assay; Topo I inhibition activity; Molecular docking; TOPOISOMERASE-I; COPPER(II) COMPLEX; ANTITUMOR PROSTAGLANDINS; DEOXYRIBONUCLEIC-ACID; POLYPYRIDYL COMPLEX; OXIDATIVE CLEAVAGE; CHEMICAL NUCLEASES; SITE-SPECIFICITY; NUCLEIC-ACIDS; INHIBITION;

D O I：

10.1016/j.ejmech.2012.01.005

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A novel heterobimetallic Cu-II-Sn-IV complex 1 bearing bioactive 1,10-phenanthroline pharmacophore ligand scaffold was synthesized and characterized by elemental analysis, IR, UV-vis spectroscopy, Mass (ESI and FAB) and X-ray crystallography. The in vitro DNA binding studies of complex 1 with CT DNA was carried out by various biophysical and molecular docking techniques which revealed that complex 1 binds to DNA through intercalation in the minor groove having AT-rich sequences. Complex 1 exhibits high chemical nuclease activity cleaving supercoiled pBR322 DNA via hydrolytic pathway which was further evidenced by T4 DNA ligase assay. The complex 1 shows high inhibitory activity against Topo I at a very low concentration (15 mu M), suggesting that complex 1 is an efficient catalytic inhibitor of human Topo I and further validated by molecular docking studies. (C) 2012 Elsevier Masson SAS. All rights reserved.

引用

页码：141 / 150

页数：10

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