Structure Effect of Some New Anticancer Pt(II) Complexes of Amino Acid Derivatives with Small Branched or Linear Hydrocarbon Chains on Their DNA Interaction

The aim of this study was to investigate the structure effect and identify the modes of binding of amino acid-Pt complexes to DNA molecule for cancer treatment. Hence, three novel water soluble platinum complexes, [Pt(phen)(R-gly)]NO3 (where phen is 1,10-phenanthroline, R-gly is methyl, amyl, and isopentyl-glycine), have been synthesized and characterized by spectroscopic methods, conductivity measurements, and chemical analysis. The anticancer activities of synthesized complexes were investigated against human breast cancer cell line of MDA-MB 231. The 50% cytotoxic concentration values were determined to be 42.5, 58, and 70 m for methyl-, amyl-, and isopentyl-gly complexes, respectively. These complexes were interacted with calf thymus DNA (ct-DNA) via positive cooperative interaction. The modes of binding of the complexes to DNA were investigated by fluorescence spectroscopy and circular dichroism in combination with a molecular docking study. The result indicates that complexes with small or branched hydrocarbon chains can intercalate with DNA. This is while amyl complexes with linear chains interacted additionally via groove binding. The results of the negative value of Gibbs energy for binding of isopentyl-platinum to DNA and those of the molecular docking were coherent. Furthermore, the docking results demonstrated that hydrophobic interaction plays an important role in the complex-DNA interaction.