Two new complexes Pt(L1)ClCl (Pt1) and Pt(L2)ClCl (Pt2), (L1 = N2,N6-bis(5-methylthiazol-2-yl)pyridine-2,6-dicarboxamide and L2 = N2,N6-di(benzodthiazol-2-yl)pyridine-2,6-dicarboxamide), were synthesized and characterized. The rate of nucleophilic substitution reactions of complexes with l-methionine (l-Met), l-cysteine (l-Cys), and guanosine-5'-monophosphate (5'-GMP) decreases in the order of biomolecules reactivity: l-Met > l-Cys >5'-GMP. The complexes exhibited moderate binding affinity for calf thymus DNA and human serum albumin. Competitive binding studies of complexes with DNA in the presence of ethidium bromide and Hoechst 33258 revealed that minor groove binding is more dominant over intercalation. Pt1 was more selective and effective in decreasing the viability of 4T1 breast cancer cells by promoting both early- and late-stage apoptosis. The in vivo findings reinforced these results, demonstrating that Pt1 significantly reduced tumor growth while exhibiting minimal systemic toxicity. Molecular docking complemented experimental data, confirming DNA and HSA binding for both complexes, while Pt1 aligned better with pro-apoptotic activity under physiological conditions.
Nićiforović et al. (Fri,) studied this question.