title: Synthesis and structure elucidation of a cobalt(II) complex as topoisomerase I inhibitor: in vitro DNA binding, nuclease and RBC hemolysis.
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.
authors.affiliation: Department of Chemistry, Indian Institute of Technology Kanpur, UP 208016, India.
authors.forename: Musheer
authors.initials: M
authors.lastname: Ahmad
authors.affiliation: Department of Chemistry, Aligarh Muslim University, Aligarh, UP 202002, India.
authors.forename: Mohd
authors.initials: M
authors.lastname: Afzal
authors.affiliation: Department of Chemistry, Aligarh Muslim University, Aligarh, UP 202002, India. Electronic address: tsartaj62@yahoo.com.
authors.forename: Sartaj
authors.initials: S
authors.lastname: Tabassum
authors.affiliation: Faculty of Chemistry, University of Wroclaw, 14 F. Joliot-Curie Street, 50-383 Wrocław, Poland.
authors.forename: Bożena
authors.initials: B
authors.lastname: Kalińska
authors.affiliation: Faculty of Chemistry, University of Wroclaw, 14 F. Joliot-Curie Street, 50-383 Wrocław, Poland.
authors.forename: Jerzy
authors.initials: J
authors.lastname: Mrozinski
authors.affiliation: Department of Chemistry, Indian Institute of Technology Kanpur, UP 208016, India. Electronic address: pkb@iitk.ac.in.
authors.forename: Parimal K
authors.initials: PK
authors.lastname: Bharadwaj
mesh_terms: D003035:Cobalt / Q000737:chemistry* / Q000494:pharmacology; D018360:Crystallography, X-Ray; D004247:DNA / Q000378:metabolism*; D004720:Endonucleases / Q000378:metabolism*; D004912:Erythrocytes / Q000187:drug effects* / Q000201:enzymology; D006461:Hemolysis / Q000187:drug effects*; D006801:Humans; D008855:Microscopy, Electron, Scanning; D062105:Molecular Docking Simulation; D010957:Plasmids; D013057:Spectrum Analysis; D013818:Thermogravimetry; D059004:Topoisomerase I Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D059004:Topoisomerase I Inhibitors; D003035:Cobalt; D004247:DNA; D004720:Endonucleases
keywords: CT DNA binding; Molecular docking; T4 DNA ligase assay; Topo I inhibition activity; pBR322 DNA cleavage