Variation of Arene Moiety in Ruthenium (II) Arene Halido Complexes of Quinoline and Benzazole-Derived Ligands: Development and Antiprostate Cancer Potential.

Castration-resistant prostate cancer (CRPC) is an advanced, treatment-refractory disease with high mortality and limited therapeutic options, necessitating novel metallodrugs with enhanced potency and reduced toxicity. Herein, we report the design and syntheses of two quinoline-benzazole hybrid bidentate ligands-2-(1H-benzo[d]imidazol-2-yl)quinoline (L1) and 2-(quinolin-2-yl)benzo[d]thiazol (L2)-along with four new half-sandwich ruthenium(II) arene chlorido complexes of the general formula [(η6-arene)(L)RuCl]PF6, where arene = benzene (Bz) or hexamethylbenzene (Hmb), yielding complexes 1-4. The ligands and complexes were fully characterized by spectroscopic (1H/1 3C NMR, IR, UV-vis) and analytical methods (elemental analysis, ESI-MS), with aqueous stability profiles confirming their suitability for biological evaluation. Cytotoxicity assays against the PC-3 CRPC cell line identified potent antiproliferative activity in selected complexes. Mechanistic studies revealed predominant G2/M phase cell cycle arrest, induction of apoptosis, and moderate-to-strong DNA binding affinities suggestive of intercalative/groove-binding modes. These results highlight the potential of quinoline-benzazole Ru(II) arene scaffolds as promising candidates for CRPC therapy, meriting further optimization.