Novel organoruthenium complexes containing β-Diketonates: Synthesis, characterization, DNA/HSA interactions, and the impact of biocompatible ionic liquids on biological activities

Abstract

In order to discover new dual-active agents, novel ruthenium (η⁶-p-cymene) complexes of the general formula [(η⁶-p-cym)Ru(OO)Cl] with O,O-diketo ester ligands ethyl 2-hydroxy-4-aryl-4-oxobut-2-enoate (1–3), were synthesized. The complexes 1–3 were characterized by spectral techniques (UV–Vis, IR, ¹H and ¹³C NMR, and ESI-HRMS), elemental analysis, and X-ray crystallography. Based on in vitro DNA/HSA experiments, complex 1 exhibited the highest DNA/HSA-activity, suggesting that the presence of an alkene chain contributes to increased activity. The cytotoxic activity of 1–3 was evaluated in a panel of human cancer cell lines (A549, MDA-MB-231, LS-174, HeLa), and in one normal cell line (MRC-5), both in the absence and presence of biocompatible ionic liquids (BIO-ILs) such as cholinium glycinate (Cho-Gly), cholinium β-alaninate (Cho-Ala), and cholinium glutamate (Cho-Glu). Complex 1 exhibited the highest cytotoxicity and demonstrated selectivity toward HeLa cells. Additionally, its cytotoxicity was enhanced when combined with the BIO-ILs Cho-Gly and Cho-Ala. This study suggests that ionic liquids can influence the efficacy and selectivity of cancer treatments, highlighting the potential for enhancing therapeutic outcomes. However, it also emphasizes the need for a deeper understanding of BIO-IL interactions with cellular processes. Furthermore, compound 1 displayed strong antimicrobial activity against Staphylococcus aureus and Escherichia coli (MIC = 0.078 mg/mL). Among the assessed species, Candida albicans showed the highest sensitivity to antifungal activity. These results suggest that investigated compounds may have potential for further development as clinical candidates, pending additional studies.