Synthesis, characterization, antimicrobial and cytotoxic activity of novel half-sandwich Ru(II) arene complexes with benzoylthiourea derivatives

Three new ruthenium(II)-arene complexes, [Ru(η⁶-p-cymene)(L¹)Cl₂] (C1) where L¹ is N-((4 methoxyphenyl)carbamothioyl)benzamide; [Ru(η⁶-p-cymene)(L²)Cl₂] (C2) where L² is 4-(3-benzoylthioureido)benzoic acid and [Ru(η⁶-p-cymene)(L³)Cl₂] (C3) where L³ is methyl 4-(3- benzoylthioureido)benzoate have been synthetized, characterized and evaluated for their antimicrobial and anticancer activity. Characterization was performed using ¹H and ¹³C NMR, IR spectroscopy, mass spectrometry, electrical conductivity measurements and X-Ray diffraction analysis. X-Ray diffraction analysis of C1 showed typical expected "piano-stool" geometry with ruthenium coordinated to ligand via nitrogen and sulfur atoms of benzoylthiourea derivatives. Interesting, in herein described complex, upon coordination the four-membered ring was formed, instead of six-membered chelate common for this type of ligands. Cytotoxic activity was determined in human cervix adenocarcinoma (HeLa) cell line and IC₅₀ values ranged from 29.68 to 52.36 μM and the complexes were more active than related ligands (except in case of C2 where it is found that IC₅₀ value is close to IC₅₀ value of related ligand). Complex [Ru(η⁶-p-cymene)(L¹)Cl₂] (C1) expressed the highest cytotoxic activity with IC₅₀ value of 29.7 μM. Complexes and ligands were tested against nine Gram-positive and Gram-negative bacteria and one yeast- Candida albicans. Clinical Candida spp. strains from microbiological laboratories were included in testing processes as well. Minimum inhibitory concentrations values ranged from 62.5 μg/ml for complexes against Candida albicans to over 1000 μg/ml for several bacterial species.