Substitution of the chlorido ligand for PPh3 in anticancer organoruthenium complexes of sulfonamide functionalized pyridine-2-carbothioamides leads to high cytotoxic activity

• Preparation of substituted pyridinecarbothioamide ligands. • Synthesis of organoruthenium complexes. • Determination of the antiproliferative activity. • The most potent derivative shows biological activity similar to cisplatin. The functionalization of Ru(arene) complexes with bioactive moieties is a promising approach for modulating their biological properties. This strategy may result in compounds with synergistic biological effects which may be capable of overcoming major drawbacks of currently used chemotherapeutics. A series of Ru II (η 6 - p -cymene)Cl complexes 1a – 1c comprising sulfonamide and pyridine-2-carbothioamide (PCA) ligands were designed to evaluate their antiproliferative potency in cancer cells. The ligands and their corresponding organoruthenium complexes were characterized by NMR spectroscopy, elemental analysis, ESI-MS analysis and the molecular structure of 1a was determined by X-ray diffraction analysis. In vitro cytotoxic assays showed that the chlorido complexes 1a – 1c are inactive. However, the cytotoxicity was significantly improved when the labile chlorido ligand was replaced with triphenylphosphine in 2a – 2c . The most active complex 2c showed IC 50 values as low as 1.9 ± 0.5 µM in cervical carcinoma SiHa cells compared to 3.0 ± 1.1 µM for the chemotherapeutic agent cisplatin.