The current study explores the impact of cis and trans isomers of [Pt(L-ser)2] complex on their cytotoxicity and DNA binding tendencies. Hence, these isomers were synthesized with the modifications aimed at improving the established procedure, and their antiproliferative assessments were carried out on MCF-7 and HCT-116 (cancerous) as well as MCF10A and CCD-841 (normal cell lines) using identical procedures. The findings indicated the superiority of these isomers over the known antitumor compound, carboplatin, where the cis one is more favorable. DNA binding investigation were accomplished under the body conditions. The electronic absorption experiments yielded that even the low concentration of these metal complexes can denature DNA, with satisfactory binding constant. The fluorescence titration illustrated that static quenching is the predominant process in the binding, and the hydrogen bonds/van der Waals forces are the interaction types. Other investigations comprise viscosity, lipophilicity and gel electrophoresis. DFT analysis revealed that the carboxylate oxygen and nitrogen atoms are prone to participate in hydrogen bonding with DNA. Molecular docking showed the groove binding mode with DNA, mainly through hydrogen bond interactions. Molecular dynamics simulations validated the docking results over time and in a solvated environment. Additionally, QM/MM analysis revealed DNA conformational changes induced by the isomer compounds.
