title: Substitutional impact on biological activity of new water soluble Ni(II) complexes: Preparation, spectral characterization, X-ray crystallography, DNA/protein binding, antibacterial activity and in vitro cytotoxicity.
abstract: A series of new water soluble nickel(II) complexes containing triphenylphosphine and 4-methoxysalicylaldehyde-4(N)-substituted thiosemicarbazones were synthesized and characterized. Crystallographic investigations confirmed the structure of the complexes (1-4) having the general structure [Ni(4-Msal-Rtsc)(PPh3)] (Where R=H (1); CH3(2); C2H5(3); C6H5(4)) which showed that thiosemicarbazone ligands coordinated to nickel(II) ion as ONS tridentate bibasic donor. DNA/BSA protein binding ability of the ligands and their new complexes were studied by taking calf-thymus DNA (CT-DNA) and Bovine serum albumin (BSA) through absorption and emission titrations. Ethidium bromide (EB) displacement study showed the intercalative binding trend of the complexes to DNA. From the albumin binding studies, the mechanism of quenching was found as static and the alterations in the secondary structure of BSA by the compounds were confirmed with synchronous spectral studies. The binding affinity of the complexes to CT-DNA and BSA has the order of [Ni(4-Msal-etsc)(PPh3)] (3) >[Ni(4-Msal-mtsc)(PPh3)] (2) >[Ni(4-Msal-tsc)(PPh3)] (1) >[Ni(4-Msal-ptsc)(PPh3)] (4). In vitro cytotoxicity of the complexes was tested on human lung cancer cells (A549), human cervical cancer cells (HeLa), human liver carcinoma cells (Hep G2). All the complexes exhibited significant activity against three cancer cells. Among them, complex 4 exhibited almost 2.5 fold activity than cisplatin in A549 and HepG2 cell lines. In HeLa cell line, the complexes exhibited significant activity which is less than cisplatin. While comparing the activity of the complexes in A549 and HepG2 cell lines it falls in the order 4>1>2>3>cisplatin. The results obtained from DNA, protein binding and cytotoxicity studies, it is concluded that the cytotoxicity of the complexes as determined by MTT assay were not unduly influenced by the complexes having different binding efficiency with DNA and protein. The complexes exhibited good spectrum of antibacterial activity against four pathogenic bacteria such as E. faecalis (gram +ve), S. aureus (gram +ve), E. coli (gram -ve) and P. aeruginosa (gram -ve).
authors.affiliation: Department of Chemistry, Bharathiar University, Coimbatore 641 046, India.
authors.forename: C
authors.initials: C
authors.lastname: Umadevi
authors.affiliation: Department of Chemistry, Nirmala College for Women, Bharathiar University, Coimbatore 641 018, India.
authors.forename: P
authors.initials: P
authors.lastname: Kalaivani
authors.affiliation: Department of Chemistry, Durham University, Durham DH1 3LE, UK.
authors.forename: H
authors.initials: H
authors.lastname: Puschmann
authors.affiliation: Department of Biotechnology, Karunya University, Coimbatore 641114, India.
authors.forename: S
authors.initials: S
authors.lastname: Murugan
authors.affiliation: Department of Chemistry, Bharathiar University, Coimbatore 641 046, India.
authors.forename: P S
authors.initials: PS
authors.lastname: Mohan
authors.affiliation: Department of Chemistry, Bharathiar University, Coimbatore 641 046, India. Electronic address: rpnchemist@gmail.com.
authors.forename: R
authors.initials: R
authors.lastname: Prabhakaran
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D002417:Cattle; D045744:Cell Line, Tumor; D018360:Crystallography, X-Ray; D004247:DNA / Q000378:metabolism*; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D006801:Humans; D008826:Microbial Sensitivity Tests; D009532:Nickel / Q000737:chemistry / Q000494:pharmacology*; D011485:Protein Binding; D012710:Serum Albumin, Bovine / Q000378:metabolism*; D012995:Solubility; D013057:Spectrum Analysis; D014867:Water / Q000737:chemistry*
chemical_list: D000900:Anti-Bacterial Agents; D014867:Water; D012710:Serum Albumin, Bovine; D009532:Nickel; D004247:DNA
keywords: A549 cells; Antibacterial activity; CT-DNA/BSA binding; Cytotoxicity; HeLa; HepG2 cells; Nickel(II) thiosemicarbazones; Spectroscopy; X-ray crystallography