title: Synthesis, characterization; DNA binding and antitumor activity of ruthenium(II) polypyridyl complexes.
abstract: Three new ruthenium(II) polypyridyl complexes [Ru(phen)2BrIPC](2+) (1), [Ru(bpy)2 BrIPC](2+) (2) and [Ru(dmb)2BrIPC](2+) (3) where, BrIPC = (6-bromo-3-(1H-imidazo[4,5-f] [1,10]-phenanthroline, phen = 1,10-phenanthroline, bpy = 2,2' bipyridine, dmb = 4,4'-dimethyl 2,2' bipyridine, were synthesised and characterised. DNA-binding nature was investigated by spectroscopic titrations and mode of binding was assessed by viscosity measurements. The DNA-binding constants Kb of complexes 1, 2 and 3 were determined to be in the order of 10(5). Experimental results showed that these complexes interact with CT-DNA by intercalative mode. Photocleavage and antimicrobial activities were complex concentration dependent, at high concentration, high activity and vice versa. MTT assay was performed on HeLa cell lines, IC50 values of complexes in the order of 3 > 2 > 1 > cisplatin. From comet assay, cellular uptake studies, we observed that complexes could enter into the cell membrane and accumulate inside the nucleus. Molecular docking studies support the DNA binding affinity with hydrogen bonding and van der Waals attractions between base pairs and phosphate backbone of DNA with metal complexes.
authors.affiliation: Department of Chemistry, Osmania University, Hyderabad 500007, India.
authors.forename: A
authors.initials: A
authors.lastname: Srishailam
authors.affiliation: Department of Chemistry, Osmania University, Hyderabad 500007, India.
authors.forename: Nazar Mohammed
authors.initials: NM
authors.lastname: Gabra
authors.affiliation: Department of Chemistry, Osmania University, Hyderabad 500007, India.
authors.forename: Yata Praveen
authors.initials: YP
authors.lastname: Kumar
authors.affiliation: Department of Chemistry, Osmania University, Hyderabad 500007, India.
authors.forename: Kotha Laxma
authors.initials: KL
authors.lastname: Reddy
authors.affiliation: Department of Chemistry, Osmania University, Hyderabad 500007, India.
authors.forename: C Shobha
authors.initials: CS
authors.lastname: Devi
authors.affiliation: Department of Biochemistry, Osmania University, Hyderabad 500007, India.
authors.forename: D
authors.initials: D
authors.lastname: Anil Kumar
authors.affiliation: Department of Biochemistry, Osmania University, Hyderabad 500007, India.
authors.forename: Surya S
authors.initials: SS
authors.lastname: Singh
authors.affiliation: Department of Chemistry, Osmania University, Hyderabad 500007, India. Electronic address: ssnsirasani@gmail.com.
authors.forename: S
authors.initials: S
authors.lastname: Satyanarayana
mesh_terms: D015082:2,2'-Dipyridyl / Q000737:chemistry; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001665:Binding Sites; D020552:Comet Assay; D056831:Coordination Complexes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D053837:DNA Cleavage / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D006860:Hydrogen Bonding; D007700:Kinetics; D062105:Molecular Docking Simulation; D009690:Nucleic Acid Conformation; D010618:Phenanthrolines / Q000737:chemistry; D012428:Ruthenium / Q000737:chemistry*; D055672:Static Electricity
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D010618:Phenanthrolines; D015082:2,2'-Dipyridyl; D012428:Ruthenium; D004247:DNA; C025205:1,10-phenanthroline
keywords: Comet assay; DNA-binding; Docking; Intercalative; Phosphate backbone; Spectroscopic titrations