Synthesis and structure elucidation of a cobalt(II) complex as topoisomerase I inhibitor: in vitro DNA binding, nuclease and RBC hemolysis - PubMed (original) (raw)

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

Musheer Ahmad et al. Eur J Med Chem. 2014.

Abstract

Metal-based cancer chemotherapeutic agent of the type Co(II) complex [Co(mpca)₂]·H₂O (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 μM concentration and further validated by molecular docking studies.

Keywords: CT DNA binding; Molecular docking; T4 DNA ligase assay; Topo I inhibition activity; pBR322 DNA cleavage.

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Synthesis and structure elucidation of a cobalt(II) complex as topoisomerase I inhibitor: in vitro DNA binding, nuclease and RBC hemolysis - PubMed (original) (raw)