title: Dinuclear manganese(II) complexes of hexaazamacrocycles bearing N-benzoylated pendant separated by aromatic spacers: Antibacterial, DNA interaction, cytotoxic and molecular docking studies.
abstract: Three new homodinuclear manganese(II) complexes of the type [Mn2L(1-3)(ClO4)(H2O)](ClO4)3 (1-3) have been synthesized via cyclocondensation of terephthalaldehyde with three different benzoylated pendants in the presence of manganese(II) perchlorate and characterized by spectroscopic methods. Cyclic voltammetric investigation of complexes (1-3) depict two quasi-reversible one electron reduction processes in the cathodic potential region (E(1)pc=-0.73 to-0.83 V, E(2)pc=-1.31 to -1.40 V) and two quasi-reversible one electron oxidation processes in the anodic potential region (E(1)pa=1.03 to 1.10 V, E(2)pa=1.69 to 1.77 V). Electronic absorption spectra of the complexes suggested tetrahedral geometry around the central metal ion. The observed low magnetic moment values (μeff, 5.60-5.68 B.M.) of the complexes indicate the presence of an antiferromagnetic spin-exchange interaction between two metal centers, which was also supported by the broad EPR signal. All the compounds were tested for antibacterial activity against Gram (-ve) and Gram (+ve) bacterial strains. The binding studies of complexes with CT-DNA suggested minor-groove mode of interaction. Molecular docking studies were carried out in order to find the binding affinity of complexes with DNA and protein EGFR Kinase. The complexes are stabilized by additional electrostatic and van der Waals interaction with the DNA, and support minor groove mode of binding. The cleavage activity of complexes on pBR322 plasmid DNA displays efficient activity through a mechanistic pathway involving hydroxyl radicals. The cytotoxicity of complexes 2 and 3 have been tested against human liver adenocarcinoma (HepG2) cell line. Nuclear-chromatin cleavage has also been observed with propidium iodide (PI) staining and alkaline single-cell gel electrophoresis (comet assay) techniques.
authors.affiliation: Post-Graduate and Research Department of Chemistry, The New College (Autonomous), Chennai 600 014, India.
authors.forename: P
authors.initials: P
authors.lastname: Arthi
authors.affiliation: Department of Bioinformatics, School of Bioengineering, SRM University, Kattankulathur 603 203, India.
authors.forename: S
authors.initials: S
authors.lastname: Shobana
authors.affiliation: Department of Bioinformatics, Alagappa University, Karaikudi 630 004, India; Department of Animal Health and Management, Alagappa University, Karaikudi 630 004, India.
authors.forename: P
authors.initials: P
authors.lastname: Srinivasan
authors.affiliation: Department of Zoology, University of Madras, Guindy Campus, Chennai 600 025, India.
authors.forename: D
authors.initials: D
authors.lastname: Prabhu
authors.affiliation: Department of Zoology, University of Madras, Guindy Campus, Chennai 600 025, India.
authors.forename: C
authors.initials: C
authors.lastname: Arulvasu
authors.affiliation: Post-Graduate and Research Department of Chemistry, The New College (Autonomous), Chennai 600 014, India. Electronic address: akrahmanjkr@gmail.com.
authors.forename: A
authors.initials: A
authors.lastname: Kalilur Rahiman
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D001665:Binding Sites; D002470:Cell Survival / Q000187:drug effects; D020552:Comet Assay; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D053837:DNA Cleavage / Q000187:drug effects; D066246:ErbB Receptors / Q000737:chemistry / Q000378:metabolism; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D008345:Manganese / Q000737:chemistry*; D062105:Molecular Docking Simulation; D009690:Nucleic Acid Conformation; D017434:Protein Structure, Tertiary
chemical_list: D000900:Anti-Bacterial Agents; D056831:Coordination Complexes; D008345:Manganese; D004247:DNA; D066246:ErbB Receptors
keywords: Antibacterial activity; Apoptosis; DNA interaction; Mn(II) complexes; Molecular docking; Pendant-armed