Three novel dinuclear calcium(ii) complexes with 5,7-dihalo-8-quinolinolato showing potent anticancer activity

Abstract

To develop novel calcium(II) coordination compounds aimed at overcoming cisplatin (RiPt) resistance, we synthesized three dinuclear calcium(II) complexes: [Ca₂(μ₂-O)₂(dhg1)₄(CP)₂] (CaL1), [Ca₂(μ₂-O)₂(dhg2)₄(CP)₂] (CaL2), and [Ca₂(μ₂-O)₂(dhg3)₄(CP)₂] (CaL3). These contain four deprotonated 5,7-dichloro-8-quinolinol (H-dhg1), clioquinol (H-dhg2), or 5,7-dibromo-8-hydroxyquinoline (H-dhg3) ligands, respectively, and two 5-chloro-1,10-phenanthroline (CP) ligands. In vitro cytotoxicity studies of CaL1–CaL3 against cisplatin-resistant ovarian SK-OV-3/DDP (RiSK3) cancer cells and healthy (HL-7702) cells revealed promising selective cytotoxicity toward RiSK3 cells with IC₅₀ values of 0.58 ± 0.03, 0.89 ± 0.12 and 1.93 ± 0.26 μM, respectively. Notably, CaL1 and CaL2 induced not only apoptosis but also lethal mitophagy in RiSK3 cells. These findings provide a promising strategy for developing calcium(II)-8-hydroxyquinoline-based drugs capable of overcoming RiPt resistance.