ABSTRACT
Synthesis, spectral, electrochemical and single crystal X-ray diffraction data of a new series of DMSO containing bivalent ruthenium hydrazone complexes are presented. XRD data of two of the new complexes revealed an octahedral coordination around the ruthenium ion satisfied by NOS2Cl2 atoms. Electrochemical studies showed the metal centred, quasi-reversible, one-electron redox behaviour of the new complexes. The binding of these complexes with biomolecules such as calf thymus DNA (CT-DNA) and bovine serum albumin (BSA) protein investigated by different spectrophotometric methods revealed an intercalative mode of interaction. The in vitro cytotoxicity of these complexes evaluated by the MTT assay on a panel of cancer and normal cell lines indicated that the above complexes are more toxic to cancer cells with a few micromolar concentrations as the IC50 value, but are significantly less toxic to normal cell lines. The observed variations in the binding interactions and cytotoxicity of the complexes were attributed to the nature of the hydrazide moiety of the hydrazones that influences their biological activities.
Subject(s)
Antineoplastic Agents , Coordination Complexes , Dimethyl Sulfoxide , Hydrazones , Ruthenium , Animals , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Cell Line, Tumor , Cell Survival/drug effects , Coordination Complexes/chemistry , Coordination Complexes/pharmacology , DNA/metabolism , Dimethyl Sulfoxide/chemistry , Dimethyl Sulfoxide/pharmacology , Humans , Hydrazones/chemistry , Hydrazones/pharmacology , Mice , NIH 3T3 Cells , Ruthenium/chemistry , Ruthenium/pharmacology , Serum Albumin, Bovine/metabolismABSTRACT
Resistomycin, a secondary metabolite produced by Streptomyces aurantiacus AAA5. The binding interaction of resistomycin with calf thymus DNA (CT DNA) and bovine serum albumin (BSA) was investigated by spectrophotometry, spectrofluorimetry, circular dichroism (CD) and synchronous fluorescence techniques under physiological conditions in vitro. Absorption spectral studies along with the fluorescence competition with ethidium bromide measurements and circular dichroism clearly suggest that the resistomycin bind with CT DNA relatively strong via groove binding. BSA interaction results revealed that the drug was found to quench the fluorescence intensity of the protein through a static quenching mechanism. The number of binding sites 'n' and apparent binding constant 'K' calculated according to the Scatchard equation exhibit a good binding property to bovine serum albumin protein. In addition, the results observed from synchronous fluorescence measurements clearly demonstrate the occurrence of conformational changes of BSA upon addition of the test compound.
Subject(s)
DNA/metabolism , Serum Albumin, Bovine/metabolism , Streptomyces/metabolism , Animals , Benzopyrenes/metabolism , Binding Sites , Cattle , Circular Dichroism , Fluorometry , Protein Binding , Protein Conformation , Serum Albumin, Bovine/chemistryABSTRACT
Divalent Co, Ni and Cu hydrazone complexes containing [N'-(phenyl(pyridine-2-yl)methylidene) benzohydrazide] ligand were synthesised and characterised. Interactions of these complexes with DNA revealed an intercalative mode of binding between them. Further, all the hydrazone chelates showed moderate ability to cleave pUC19 DNA. Synchronous fluorescence spectra proved that the interaction of metal complexes with bovine serum albumin (BSA) resulted in a conformational change of the latter. Assay on the cytotoxicity of the above complexes against HeLa tumor cells and NIH 3T3 normal cells revealed that the complexes are toxic only against tumor cells but not to normal cells. In all the biological assays, the complex with copper ion as the metal center showed enhanced activities than the other two.
Subject(s)
Antineoplastic Agents/chemical synthesis , Coordination Complexes/chemical synthesis , Copper/chemistry , Hydrazones/chemical synthesis , Intercalating Agents/chemical synthesis , Serum Albumin, Bovine/chemistry , Animals , Antineoplastic Agents/pharmacology , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Cattle , Cobalt/chemistry , Cobalt/metabolism , Coordination Complexes/pharmacology , Copper/metabolism , Crystallography, X-Ray , DNA/metabolism , DNA Cleavage/drug effects , Female , HeLa Cells , Humans , Hydrazones/pharmacology , Intercalating Agents/pharmacology , Mice , Models, Molecular , NIH 3T3 Cells , Nickel/chemistry , Nickel/metabolism , Plasmids/metabolism , Protein Binding/drug effects , Protein Conformation/drug effects , Pyridines/chemistry , Serum Albumin, Bovine/metabolism , Spectrometry, FluorescenceABSTRACT
A new series of stable binuclear ruthenium(II) carbonyl complexes of the general formula [{RuX(CO)(EPh(3))(2)}(2)L] (where X=H or Cl; E=P or As and L=dibasic tetradentate diacetyl resorcinol (H(2)-DAR)) have been synthesised by reacting ruthenium(II) starting complexes [RuHX(CO)(EPh(3))(3)] (where X=H or Cl; E=P or As) and 4,6-diacetylresorcinol (H(2)-DAR) ligand in benzene medium. The structure of the new binuclear ruthenium(II) carbonyl complexes was established using elemental analysis, spectra (FT-IR, UV-vis and (1)H NMR), electrochemical and thermal studies. In these reactions, the 4,6-diacetylresorcinol (H(2)-DAR) ligand behaves as a binegative tetradentate chelating ligand coordinating through O,O atoms of both the carbonyl and phenolic C-O groups by replacing a molecule of PPh(3)/AsPh(3) and a hydride ion from the starting complexes. Further, all these complexes were also employed as new catalysts for the oxidation of primary and secondary alcohols in the presence of N-methylmorpholine-N-oxide (NMO) as a more viable co-oxidant. The free ligand and their metal complexes have also been screened for their antibacterial activity against the growth of gram +ve and gram -ve bacterial cultures.
