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 [(η6-p-cymene)RuL]Cl (6) and [(η6-p-cymene)RuL]PF6 (L = [2-C8H5N(Ph2PNC6H4XR)]− [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 μg mL−1|0.717–3.973 μM) against the three cancer cell lines but only complexes 9–11 showed poor cytoxicity in normal fibroblasts (IC50: 6.069–7.227 μg mL−1|6.898–8.214 μM). 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.