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

Article abstract of DOI:10.1016/j.ejmech.2013.08.025

Neutral iridium(III) complexes of the type [Ir(η⁵-C ₅Me₅)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{Ph₂PCH ₂SPh-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{Ph ₂PCH₂S(O)Ph-κP}] (2), with ligand L2 κP coordinated containing a pendent sulfinyl group, is the most active one (IC ₅₀ 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.