Anticancer Potential of (Pentamethylcyclopentadienyl)chloridoiridium(III) Complexes Bearing kappa P and kappa P,kappa S-Coordinated Ph2PCH2CH2CH2S(O)(x)Ph (x=0-2) Ligands

Gerd Ludwig, Ivan Randelovic, Danijela Maksimovic-Ivanic, Sanja Mijatovic, Mirna Z. Bulatovic, Djordje Miljkovic, Marcus Korb, Heinrich Lang, Dirk Steinborn, Goran N. Kaluderovic

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Iridium(III) complexes of the type [Ir(eta(5)-C5Me5)Cl-2{Ph2PCH2-CH2CH2S(O)(x)Ph-kappa P}] (x=0-2; 1-3) and [Ir(eta(5)-C5Me5)Cl{Ph2PCH2-CH2CH2S(O)(x)Ph-kappa P,kappa S}][PF6] (x=0-1; 4 and 5) with 3-(diphenyl-phosphino)propyl phenyl sulfide, sulfoxide, and sulfone ligands Ph2PCH2CH2CH2S(O)(x)Ph were designed, synthesized, and characterized fully, including X-ray diffraction analyses for complexes 3 and 4. In vitro studies against human thyroid carcinoma (8505C), submandibular carcinoma (A253), breast adenocarcinoma (MCF-7), colon adenocarcinoma (SW480), and melano-ma (518A2) cell lines provided evidence for the high biological potential of the neutral and cationic iridium(III) complexes. Neutral iridium(III) complex 5 proved to be the most active, with IC50 values up to about 0.1 mu m, representing activities of up to one order of magnitude higher than cisplatin. Using 8505C cells, apoptosis was shown to be the main mechanism through which complex 5 exerts its tumoricidal action. The described iridium(III) complexes represent potential leads in the search for novel metal-based anticancer agents.

Original languageEnglish
Pages (from-to)1586-1593
Number of pages8
Issue number7
Publication statusPublished - Jul 2014
Externally publishedYes

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