Synthesis and antitumor mechanisms of two novel platinum(ii) complexes with 3-(2′-benzimidazolyl)-7-methoxycoumarin

Abstract

Two novel platinum(II) complexes, [PtCl₂(H-MeOBC)(DMSO)] (Pt1) and [Pt₂Cl₃(MeOBC)(DMSO)₂] (Pt2), with 3-(2′-benzimidazolyl)-8-methoxycoumarin (H-MeOBC) as the ligand were synthesized and evaluated for their antiproliferative activity. Among all the tumor cells, dual-Pt(II) complex Pt2 exhibited the most potent activity, with an IC₅₀ value of 0.5 ± 0.2 μM against cisplatin-resistant SK-OV-3/DDP cancer cells. In the case of SK-OV-3/DDP cells, Pt2 displayed a 20.1–196.0-fold increased activity when compared with cisplatin, H-MeOBC and Pt1. Importantly, Pt1 and Pt2 displayed low inhibitory rates against normal HL-7702 cells. Further investigation revealed that Pt2 is a novel telomerase inhibitor binding to c-myc promoter elements. Mechanistic studies demonstrated that dual-Pt(II) complex Pt2 arrests the cell cycle at the G2/M phase and induces apoptosis and causes mitochondrial dysfunction.