title: Theoretical calculations, DNA interaction, topoisomerase I and phosphatidylinositol-3-kinase studies of water soluble mixed-ligand nickel(II) complexes.
abstract: Eight water soluble mixed-ligand nickel(II) complexes of the type [NiL(1-4)(diimine)H2O]·(ClO4)2, (1-8) where L(1-4) = 2-((2-(piperazin-1-yl)ethylimino)methyl)-4-substituted phenols, and diimine = 2,2'-bipyridyl (bpy) or 1,10-phenanthroline (phen) were synthesized and characterized by elemental analysis and spectroscopic methods. The uncoordinated perchlorate anions was ascertained form IR spectra of the complexes, and the absorption spectra reveal the octahedron geometry around nickel(II) ion with tridentate Schiff base ligand, diimine and a coordinated water molecule. Cyclic voltammograms of the complexes indicate the one-electron irreversible processes in the cathodic and anodic region. In vitro antioxidant activity proved the significant radical scavenging activity of the complexes against DPPH radical. The groove/electrostatic binding nature of complexes with CT-DNA (calf thymus deoxyribonucleic acid) were affirmed by absorption, hydrodynamic and voltammetric titration experiments and docking analysis. All the complexes exhibit significant cleavage activity on plasmid DNA via hydrolytic and oxidatively, in which the oxidative mechanism involves hydroxyl radicals and supports the possibility of minor-groove binding. The complex 4 shows significant topoisomerase I (Topo-I) inhibitory activity. The molecular modeling analysis of complexes with phosphatidylinositol-3-kinase (PI3K) receptor indicate the hydrogen bonding with Met1039, Asp837 and Leu1027, and hydrophobic interactions with Ser488, Asn498, Asp500, Gln662, Lys668, Ile844, Ile847, Ile850, Val941, Leu942, Leu1020, Met1034, Leu1035, Thr1037, Met1039, Gln1041 and Ile1051 of subdomain IIA of BSA. The complexes show σ-π interaction between diimines and amino groups of Leu1030 and Arg839.
authors.affiliation: Post-Graduate and Research Department of Chemistry, The New College (Autonomous), Chennai 600 014, India.
authors.forename: Perumal
authors.initials: P
authors.lastname: Gurumoorthy
authors.affiliation: Post-Graduate and Research Department of Chemistry, The New College (Autonomous), Chennai 600 014, India.
authors.forename: Dharmasivam
authors.initials: D
authors.lastname: Mahendiran
authors.affiliation: Post-Graduate and Research Department of Chemistry, The New College (Autonomous), Chennai 600 014, India. Electronic address: akrahmanjkr@gmail.com.
authors.forename: Aziz
authors.initials: A
authors.lastname: Kalilur Rahiman
mesh_terms: D000975:Antioxidants; D056831:Coordination Complexes / Q000737:chemistry / Q000494:pharmacology*; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D053837:DNA Cleavage; D004264:DNA Topoisomerases, Type I / Q000235:genetics / Q000378:metabolism*; D055664:Electrochemical Techniques; D006801:Humans; D006860:Hydrogen Bonding; D008958:Models, Molecular; D015394:Molecular Structure; D009532:Nickel / Q000737:chemistry*; D009690:Nucleic Acid Conformation; D058539:Phosphatidylinositol 3-Kinase / Q000235:genetics / Q000378:metabolism*; D011487:Protein Conformation; D012710:Serum Albumin, Bovine; D013057:Spectrum Analysis; D013329:Structure-Activity Relationship; D059003:Topoisomerase Inhibitors / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D056831:Coordination Complexes; D059003:Topoisomerase Inhibitors; D012710:Serum Albumin, Bovine; D009532:Nickel; D004247:DNA; D058539:Phosphatidylinositol 3-Kinase; D004264:DNA Topoisomerases, Type I
keywords: Calf thymus DNA; DNA cleavage activity; PI3K receptor; Theoretical calculations; Topoisomerase I inhibitors; Water soluble complexes