Molecular drug design, synthesis and crystal structure determination of CuII-SnIV heterobimetallic core: DNA binding and cleavage studies.
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 μM), suggesting that complex 1 is an efficient catalytic inhibitor of human Topo I and further validated by molecular docking studies.
Department of Chemistry, Aligarh Muslim University, Aligarh 202002, India. farukh_arjmand@yahoo.co.in
Farukh
F
Arjmand
Shazia
S
Parveen
Mohd
M
Afzal
Loic
L
Toupet
Taibi
T
Ben Hadda
D000818:Animals; D002417:Cattle; D056831:Coordination Complexes / Q000737:chemistry* / Q000494:pharmacology; D003300:Copper / Q000737:chemistry* / Q000494:pharmacology; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D053837:DNA Cleavage / Q000187:drug effects*; D004264:DNA Topoisomerases, Type I / Q000378:metabolism; D015195:Drug Design; D006801:Humans; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D010618:Phenanthrolines / Q000737:chemistry* / Q000494:pharmacology; D014001:Tin / Q000737:chemistry* / Q000494:pharmacology; D059004:Topoisomerase I Inhibitors / Q000737:chemistry / Q000494:pharmacology
D056831:Coordination Complexes; D010618:Phenanthrolines; D059004:Topoisomerase I Inhibitors; D014001:Tin; D003300:Copper; D004247:DNA; C427203:calf thymus DNA; D004264:DNA Topoisomerases, Type I; C528909:TOP1 protein, human; C025205:1,10-phenanthroline