Evaluation of DNA binding, DNA cleavage, protein binding and in vitro cytotoxic activities of bivalent transition metal hydrazone complexes

• Published in: European journal of medicinal chemistry Vol. 46; no. 8; pp. 3376 - 3387
• Main Authors: Krishnamoorthy, P., Sathyadevi, P., Cowley, Alan H., Butorac, Rachel R., Dharmaraj, N.
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Masson SAS 01-08-2011; Elsevier
• Subjects: Animals; Antineoplastic agents; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - pharmacology; Biological and medical sciences; Breast Neoplasms - drug therapy; Breast Neoplasms - pathology; Cattle; Cobalt - chemistry; Cobalt - metabolism; Coordination Complexes - chemical synthesis; Coordination Complexes - pharmacology; Copper - chemistry; Copper - metabolism; Crystal structure; Crystallography, X-Ray; Cytotoxicity; DNA - metabolism; DNA Cleavage - drug effects; DNA interaction; Female; General aspects; HeLa Cells; Humans; Hydrazones - chemical synthesis; Hydrazones - pharmacology; Intercalating Agents - chemical synthesis; Intercalating Agents - pharmacology; Medical sciences; Metal complexes; Mice; Models, Molecular; Nickel - chemistry; Nickel - metabolism; NIH 3T3 Cells; Pharmacology. Drug treatments; Plasmids - metabolism; Protein binding; Protein Binding - drug effects; Protein Conformation - drug effects; Pyridines - chemistry; Serum Albumin, Bovine - chemistry; Serum Albumin, Bovine - metabolism; Spectrometry, Fluorescence; Cytotoxicity; Metal complexes; DNA interaction; Crystal structure; Protein binding; Tertiary phosphine; Uterine cervix; Fluorescence spectrometry; Pyridine derivatives; Cleavage; Hydrazone; Tumor cell; Human; Rodentia; Organic ligand; Transition metal Complexes; In vitro; Hela cell line; Biological activity; Protein; Absorption spectrometry; Vertebrata; Biological fixation; Mammalia; Cell line; Mouse; DNA; Fibroblast; Crystalline structure
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2011.05.001

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.
Synthesis, structural elucidation and interaction with DNA, protein, cytotoxicity studies were carried out on biologically important transition metal hydrazone complexes.
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► Synthesis of new transition metal hydrazone complexes with octahedral geometry. ► All the new complexes showed significant interaction with both DNA and protein. ► Cytotoxicity results proved their efficacy against HeLa tumor cells.