title: Cobalt(III) complexes as potential anticancer agents: Physicochemical, structural, cytotoxic activity and DNA/protein interactions.
abstract: Cobalt(III) complexes (1-3) such as [Co(acac)(bpy)(N3)2·H2O] 1, [Co(acac)(en)(N3)2] 2, and [Co(acac)(2-pic)(N3)2] 3 (where, acac=acetylacetone, bpy=2.2'-bipyridine, en=ethylenediamine, 2-pic=2-picolylamine and NaN3=sodium azide) were synthesized and characterized. The structure of complexes (1-3) has been determined by single crystal X-ray diffraction studies and the configuration around cobalt(III) ion was distorted octahedral coordination geometry. Density functional theory calculations were performed to examine the molecular geometry and frontier molecular orbital properties of complexes (1-3). DNA binding properties of the cobalt(III) complexes with calf thymus DNA (CT-DNA) were investigated by UV-visible absorption, fluorescence, circular dichroism spectroscopy and viscosity measurements. The docking studies showed the preferred orientation of sterically acceptable Co(III) complexes (1, 2) inside the DNA through the mode of intercalation, whereas complex 3 exhibited minor groove binding modes. The intrinsic binding constants Kb of complexes (1-3) with CT-DNA were in the following order 1>3>2. Complexes (1-3) exhibit a good binding propensity to bovine serum albumin (BSA) and gel electrophoresis assay demonstrated that the complexes (1-3) promote the cleavage of the pBR322 DNA in the presence of 3-mercaptopropionic acid (MPA) and cleavage process was found to proceed by singlet oxygen cleavage mechanism. Further, the in vitro cytotoxicity studies of complexes (1-3) were tested on human breast cancer cell line (MCF-7).
authors.affiliation: Department of Industrial Chemistry, Alagappa University, Karaikudi 630 003, India.
authors.forename: V
authors.initials: V
authors.lastname: Thamilarasan
authors.affiliation: Department of Chemistry, DDE, Alagappa University, Karaikudi 630 003, India. Electronic address: nsvelan1975@yahoo.com.
authors.forename: N
authors.initials: N
authors.lastname: Sengottuvelan
authors.affiliation: Department of Bioinformatics, Alagappa University, Karaikudi 630 003, India.
authors.forename: A
authors.initials: A
authors.lastname: Sudha
authors.affiliation: Department of Animal Health and Management, Alagappa University, Karaikudi 630 003, India.
authors.forename: P
authors.initials: P
authors.lastname: Srinivasan
authors.affiliation: Department of Physics, CPCL Polytechnic College, Chennai 600 068, India.
authors.forename: G
authors.initials: G
authors.lastname: Chakkaravarthi
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity; D001665:Binding Sites; D002417:Cattle; D002470:Cell Survival / Q000187:drug effects; D002942:Circular Dichroism; D003035:Cobalt / Q000737:chemistry*; D056831:Coordination Complexes / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D053837:DNA Cleavage / Q000187:drug effects; D004587:Electrophoresis, Agar Gel; D006801:Humans; D061986:MCF-7 Cells; D008968:Molecular Conformation; D062105:Molecular Docking Simulation; D009690:Nucleic Acid Conformation; D011485:Protein Binding; D012710:Serum Albumin, Bovine / Q000737:chemistry / Q000378:metabolism*; D013056:Spectrophotometry, Ultraviolet; D014783:Viscosity
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D012710:Serum Albumin, Bovine; D003035:Cobalt; D004247:DNA; C427203:calf thymus DNA
keywords: Biological activities; Cobalt(III) complexes; DFT calculation; Molecular modeling; Sodium azide