Synthesis, characterization and cytotoxic activity of cationic half-sandwich Ru(ii) complexes stabilized by iminophosphorane N,N,S and N,N,Se tridentate ligands

Five new structurally related half-sandwich cationic Ru(ii) complexes of general formula [(eta(6)-p-cymene)RuL]Cl (6) and [(eta(6)-p-cymene)RuL]PF6 (L = [2-C8H5N(Ph2P = NC6H4XR)](-) [R = C6H5, X = S (9), and Se (6, and 10); R = CH3, X = S (11), and Se (12)]) were designed and synthesized in search of new ruthenium anticancer drugs. The complexes were fully characterized by elemental analysis and various spectral methods (multinuclear NMR, and MS). The solid-state molecular structures of complexes 6, 9, and 10 were determined by X-ray crystallography and confirm the presence of pseudo-octahedral geometry around ruthenium and the facial tridentate N,N,X coordination of the iminophosphorane ligands. Solubility tests have shown compounds 9-12 to be highly soluble in polar solvents (DMSO, DMF, THF, and CH2Cl2), but insoluble in water or mixtures of DMSO/water. Different surfactants have been tested to resolve this issue, and only Tween 80 advantageously prevented precipitation in aqueous medium, and allowed for cytotoxic evaluation of complexes 9-12 using sulforhodamine B (SRB) colorimetric assay against breast carcinoma (MCF-7), prostate carcinoma (PC-3), and cervical carcinoma (SiHa) along with noncancerous HFF cells (human foreskin fibroblasts), using cisplatin as the reference standard drug. All four complexes showed high cytotoxic effects (IC50: 0.664-3.496 mu g mL(-1)|0.717-3.973 mu M) against the three cancer cell lines but only complexes 9-11 showed poor cytoxicity in normal fibroblasts (IC50: 6.069-7.227 mu g mL(-1)|6.898-8.214 mu M). Complex 10 showed a high selectivity index (SI > 3) for the three cancer types and appeared as a promising cancer therapeutic candidate worthy of further investigation.