Synthesis, structural characterization, and cytotoxic evaluation of monofunctional cis-[Pt(NH3)2(N7-guanosine/2′-deoxyguanosine)X] (X = Cl, Br, I) complexes with anticancer potential

Abstract

A series of new monofunctional platinum(II) complexes of the type cis-[Pt(NH₃)₂(N7-guanosine/2′-deoxyguanosine)X] (X = Cl, Br, I) were synthesized and characterized using NMR spectroscopy, mass spectrometry, and ICP-atomic emission spectroscopy. These complexes are designed to address the limitations of conventional bifunctional platinum-based drugs, such as cisplatin, which include issues with cytotoxicity and selectivity towards cancer cells. By incorporating guanosine or 2′-deoxyguanosine ligands and varying halido substituents, the study investigated how structural modifications influence the selectivity and cytotoxicity of the different analogues. To evaluate the anticancer potential of the newly synthesized platinum derivatives, various cancer cell lines were tested, including renal (Caki-1), uterine cervix (HeLa), breast (MCF-7), lymphoma (Raji), and mesothelioma (ZL-34). Additionally, selectivity against tumor cells was assessed by comparing their cytotoxic effects to those in the healthy, immortalized HK-2 cell line, a proximal tubular cell line derived from a normal human adult male kidney. Cytotoxicity analysis revealed that bromido-substituted Pt(II) complexes exhibited superior cytotoxicity across several cancer cell lines, particularly in HeLa and Raji cells, compared to their chlorido- and iodido-substituted counterparts. The iodido complexes exhibited higher efficacy against MCF-7 breast cancer cells, suggesting tumor-specific selectivity. Notably, these complexes demonstrated lower cytotoxicity in healthy cells compared to most of the tested cancer cell lines, as reflected by generally favorable selectivity indices (SI) relative to cisplatin.