Organoruthenium(II) complexes with adamantane-thiourea ligands: structural and biological insights.

Organometallic ruthenium complexes have gained significant attention as promising anticancer agents due to their favorable properties in medicinal chemistry. In this study, four adamantane-N-acylthiourea-based ligands (ADL1-ADL4) and their corresponding Ru(η6-p-cymene) complexes (RuAD1-RuAD4) were synthesized and characterized using 13C{1H} NMR, FT-IR, UV-vis spectroscopy, and ESI (HR)-MS. Additionally, the structures of all complexes were confirmed through single-crystal X-ray diffraction analysis. The in vitro cytotoxicity of the compounds was evaluated against human melanoma (A375), triple-negative breast cancer (MDA-MB-231), and colon cancer (HCT116 and SW620) cell lines, resulting in the selection of RuAD1 for further studies due to its superior anticancer activity. Further investigations on A375 cells showed that adamantane-ruthenium complexes exhibited stronger cytotoxicity than their corresponding ligands and other cell lines, leading to pronounced morphological alterations, inhibition of migration, and induction of apoptosis. Western blot analysis indicated that these effects were likely mediated through activation of intrinsic, mitochondrial-dependent apoptotic pathways. Additionally, in silico ADMET analysis supported the biological findings, identifying RuAD1 as having the most favorable pharmacokinetic profile among the tested compounds.