title: Molecular drug design, synthesis and structure elucidation of a new specific target peptide based metallo drug for cancer chemotherapy as topoisomerase I inhibitor.
abstract: To evaluate the biological preference of metallopeptide drugs in cancer cells, a new dinuclear copper(II) complex [Cu(2)(glygly)(2)(ppz)(H(2)O)(4)]·2H(2)O (1) (glygly = glycyl glycine anion and ppz = piperazine), was designed and synthesized as topoisomerase I inhibitor. The structural elucidation of the complex was done by elemental analysis, spectroscopic methods and single crystal X-ray diffraction. The in vitro DNA binding studies of complex 1 with CT DNA were carried out by employing different optical methods viz. UV-vis, fluorescence and circular dichroism. The molecular docking technique was also utilized to ascertain the mechanism and mode of action towards the molecular target DNA and enzymes. Complex 1 cleaves pBR322 DNA via an oxidative mechanism and strongly binds to the DNA minor groove. Furthermore, complex 1 exhibits significant inhibitory effects on the catalytic activity of topoisomerase I at a very low concentration, ~12.5 μM, in addition to its excellent SOD mimics (IC(50)~0.086 μM).
authors.affiliation: Department of Chemistry, Aligarh Muslim University, Aligarh 202201, UP, India. tsartaj62@yahoo.com
authors.forename: Sartaj
authors.initials: S
authors.lastname: Tabassum
authors.forename: Waddhaah M
authors.initials: WM
authors.lastname: Al-Asbahy
authors.forename: Mohd
authors.initials: M
authors.lastname: Afzal
authors.forename: Farukh
authors.initials: F
authors.lastname: Arjmand
authors.forename: Vivek
authors.initials: V
authors.lastname: Bagchi
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry*; D003300:Copper / Q000737:chemistry*; D004247:DNA / Q000737:chemistry; D053837:DNA Cleavage; D015195:Drug Design; D006033:Glycylglycine / Q000737:chemistry*; D015394:Molecular Structure; D009580:Nitroblue Tetrazolium / Q000737:chemistry; D013482:Superoxide Dismutase / Q000737:chemistry; D059004:Topoisomerase I Inhibitors / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D059004:Topoisomerase I Inhibitors; D006033:Glycylglycine; D009580:Nitroblue Tetrazolium; D003300:Copper; D004247:DNA; D013482:Superoxide Dismutase