Synthesis, structure and multi-therapeutic activities of econazole-containing ruthenium (II) mixed-ligand complexes: Anticancer, antimicrobial and in silico ADME profiles

A series of mixed-ligand ruthenium (II) complexes [RuCl(ecz)(P P)(N N)]PF 6 ( 3a–3f ) were synthesized with econazole (ecz) as bioactive ligand, alongside phosphine (PPh 3 , dppb, dppf) and nitrogen (bipy, phen) donors. Characterized by elemental analysis, FTIR, NMR, UV–vis, HRMS, TGA, and X-ray diffraction, they showed stable distorted octahedral geometry. Biological evaluations demonstrated that most complexes (particularly 3c ) exhibited potent and selective cytotoxicity against A549, U251, and LLC cancer cells, with superior anticancer activity to cisplatin while showing lower toxicity toward normal cells. Mechanistically, complex 3c induces cell death via dual pathways of cell membrane disruption and intracellular ROS accumulation. In antimicrobial assays, most complexes enhanced econazole's activity, with 3   f showing notable improvements that include efficacy against econazole-resistant S. aureus and heightened antifungal activity against C. albicans . In silico ADME studies revealed favorable bioavailability and CYP3A4 non-inhibition in 3b, 3c, 3e, 3   f, supporting their potential as multi-functional metallodrug candidates.