Biological activity of neutral and cationic iridium(III) complexes with kappa P and kappa P,kappa S coordinated Ph2PCH2S(O)(x)Ph (x=0-2) ligands
2013
Authors:
Ludwig, GerdMijatović, Sanja
Ranđelović, Ivan
Bulatović, Mirna Z.
Miljković, Đorđe
Maksimović-Ivanić, Danijela
Korb, Marcus
Lang, Heinrich
Steinborn, Dirk
Kaluđerović, Goran N.
Document Type:
Article (Published version)
Metadata
Show full item recordAbstract:
Neutral iridium(III) complexes of the type [Ir(eta(5)-C5Me5)Cl-2{Ph2PCH2S(O)(x)Ph-kappa P}] (1-3) with diphenylphosphino-functionalized methyl phenyl sulfides, sulfoxides, and sulfones Ph2PCH2S(O)(x)Ph (x = 0, L1; 1, 12; 2, L3) and the cationic complex [Ir(eta(5)-C5Me5)Cl(Ph2PCH2SPh-kappa P,kappa S}][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(eta(5)-C5Me5)Cl-2{Ph2PCH2S(O)Ph-kappa P}] (2), with ligand L2 kappa P coordinated containing a pendent sulfinyl group, is the most active one (IC50 values of about 3 mu M), 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. (C) 2013 Elsevier Masson SAS. All rights reserved.