Platinum(ii) complexes of fluorinated pyrrole carbothioamides: enhanced anticancer activity and overcoming cisplatin resistance

Abstract

A series of fluorinated pyrrole-derived thioamide ligands was synthesized via a solvent-free reaction of (substituted) pyrrole with various aryl isothiocyanates. Subsequent reactions of these ligands with cis-[PtCl₂(PPh₃)₂] afforded a set of charge-neutral platinum(II) complexes, featuring a variety of fluorine-containing substituents on the phenyl ring of the ligand. All compounds were characterized by NMR spectroscopy and electrospray ionization-mass spectrometry. Single-crystal X-ray diffraction analysis of a representative complex revealed that the ligand coordinated to the platinum center in a bidentate fashion through the deprotonated pyrrole nitrogen and the sulfur atom of the thioamide group, forming a five-membered chelate ring. The antiproliferative activity of selected ligands and their corresponding Pt(II) complexes was evaluated against HCT116, NCI-H460, A2780, and A2780cis human cancer cell lines, and significantly increased potency was found for a Pt complex as compared to its ligand.