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

Abstract

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 RuII(η6-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 IC50 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.