Synthesis, Characterization, and Cytotoxicity Evaluation of Novel Water‐Soluble Cationic Platinum(II) Organometallic Complexes with Phenanthroline and Imidazolic Ligands

Abstract

AbstractPlatinum‐based chemotherapeutic agents are widely used in the treatment of cancer. However, their effectiveness is limited by severe adverse reactions, drug resistance, and poor water solubility. This study focuses on the synthesis and characterization of new water‐soluble cationic monofunctional platinum(II) complexes starting from the [PtCl(η1‐C2H4OEt)(phen)] (1, phen=1,10‐phenanthroline) precursor, specifically [Pt(NH3)(η1‐C2H4OEt)(phen)]Cl (2), [Pt(1‐hexyl‐1H‐imidazole)(η1‐C2H4OEt)(phen)]Cl (3), and [Pt(1‐hexyl‐1H‐benzo[d]imidazole)(η1‐C2H4OEt)(phen)]Cl (4), which deviate from traditional requirements for antitumor activity. These complexes were evaluated for their cytotoxic effects in comparison to cisplatin, using immortalized cervical adenocarcinoma cells (HeLa), human renal carcinoma cells (Caki‐1), and normal human renal cells (HK‐2). While complex 2 showed minimal effects on the cell lines, complexes 3 and 4 demonstrated higher cytotoxicity than cisplatin. Notably, complex 4 displayed the highest cytotoxicity in both cancer and normal cell lines. However, complex 3 exhibited the highest selectivity for renal tumor cells (Caki‐1) among the tested complexes, compared to healthy cells (HK‐2). This resulted in a significantly higher selectivity than that of cisplatin and complex 4. Therefore, complex 3 shows potential as a leading candidate for the development of a new generation of platinum‐based anticancer drugs, utilizing biocompatible imidazole ligands while demonstrating promising anticancer properties.