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

Three new ruthenium(II)-arene complexes, [Ru(eta(6)-p-cymene)(L-1)Cl-2] (C1) where L-1 is N-((4 methoxyphenyl) carbamothioyl)benzamide; [Ru(eta(6)-p-cymene)(L-2)Cl-2] (C2) where L-2 is 4-(3-benzoylthioureido)benzoic acid and [Ru(eta(6)-p-cymene)(L-3)Cl-2] (C3) where L-3 is methyl 4-(3-benzoylthioureido)benzoate have been synthetized, characterized and evaluated for their antimicrobial and anticancer activity. Characterization was performed using H-1 and C-13 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 mu M 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(eta(6)-p-cymene)(L-1)Cl-2] (C1) expressed the highest cytotoxic activity with IC50 value of 29.7 mu M. 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 mu g/ml for complexes against Candida albicans to over 1000 mu g/ml for several bacterial species.