The ionic rhodium(III) and iridium(III) complexes of a new 9-aldehyde pyrimidylanthrahydrazone ligand: synthesis, crystal structure and anticancer mechanism studies

A new 9-aldehyde pyrimidylanthrahydrazone ligand (AMPAH) and its ionic Rh(III)/Ir(III) complexes were synthesized and evaluated for their potential as anticancer agents. Structural characterization by single-crystal X-ray diffraction analysis confirmed the very similar octahedral geometry for both complexes, with coordination involving DMSO and Cl⁻ moieties. Competitive DNA-binding assay suggested the effectively intercalative binding mode, by achieving the similar quenching efficiency of 83% and 84% for AMPAH-Rh and AMPAH-Ir, respectively, at quite low [GelRed]/[DNA]/[complex] molar ratio of ca. 1/10/0.3. Gel electrophoresis further confirmed the dual targets of DNA and topoisomerase I (Topo I), with AMPAH-Ir showing superior Topo I inhibition compared to AMPAH-Rh. In vitro cytotoxicity studies highlighted the selective activity of AMPAH-Ir against cancer cell lines T-24 (IC 50  = 9.05 μM) and NCI-H460 (IC 50  = 10.98 μM), surpassing the efficacy of cisplatin. Mechanistic studies revealed significant nuclear accumulation of AMPAH-Ir, together with G1-phase cell cycle arrest (59.19% at 12 μM) and early-phase apoptosis induction ( ca. 20% at 9 μM). Collectively, these results indicate that AMPAH-Ir represents a promising dual-targeting anticancer agent with and satisfying cytotoxic selectivity.