Biological activity of neutral and cationic iridium(III) complexes with κP and κP,κS coordinated Ph2PCH2S(O)xPh (x = 0–2) ligands

Neutral iridium(III) complexes of the type [Ir(η5-C5Me5)Cl2{Ph2PCH2S(O)xPh-κP}] (1−3) with diphenylphosphino-functionalized methyl phenyl sulfides, sulfoxides, and sulfones Ph2PCH2S(O)xPh (x = 0, L1; 1, L2; 2, L3) and the cationic complex [Ir(η5-C5Me5)Cl{Ph2PCH2SPh-κP,κS}][PF6] (4) were synthesized and fully characterized analytically and spectroscopically. Furthermore, the structure of 2 was determined by X-ray diffraction analysis. The biological potential of the neutral and cationic iridium(III) complexes was tested in vitro against the cell lines 8505C, A253, MCF-7, SW480 and 518A2. Complex [Ir(η5-C5Me5)Cl2{Ph2PCH2S(O)Ph-κP}] (2), with ligand L2 κP coordinated containing a pendent sulfinyl group, is the most active one (IC50 values of about 3 μM), thus, with activities comparable to cisplatin. Complex 2 proved to have an even a higher antiproliferative activity than cisplatin against 8505C and SW480 cell lines, used as a model system of highly anaplastic cancers with low sensitivity to conventional chemotherapeutics such as cisplatin. Additional experiments demonstrated that apoptosis and autophagic cell death contribute to the drug's tumoricidal action. [Display omitted] The biological potential of iridium(III) complexes of the type [Ir(η5-C5Me5)Cl2{Ph2PCH2S(O)xPh-κP}] (x = 0–2) and [Ir(η5-C5Me5)Cl{Ph2PCH2SPh-κP,κS}][PF6] even against cisplatin-resistant tumor cell lines is presented. Furthermore, structure–activity relationships and the tumoricidal action are discussed. •The biological potential of Ir(III) complexes with Ph2PCH2S(O)xPh ligands is reported.•Activity against cisplatin-resistant (8505C, SW480) cell lines was investigated.•Complex with Ph2PCH2SPh was more active than cisplatin against 8505C and SW480 cells.•Structure–activity relationships as well as the drug's tumoricidal action are discussed.