Anticancer Potential of (Pentamethylcyclopentadienyl)chloridoiridium(III) Complexes Bearing κP and κP, κS‐Coordinated Ph2PCH2CH2CH2S(O)xPh (x=0–2) Ligands. Issue 7 (27th January 2014)

• Record Type: Journal Article
• Authors: Ludwig, Gerd; Ranđelović, Ivan; Maksimović‐Ivanić, Danijela; Mijatović, Sanja; Bulatović, Mirna Z.; Miljković, Djordje; Korb, Marcus; Lang, Heinrich; Steinborn, Dirk; Kaluđerović, Goran N.
• Is Part Of: ChemMedChem. Volume 9:Issue 7(2014:Jul.)
• Page Start: 1586
• Page End: 1593
• Publication Date: 2014-01-27
• Subjects: Pharmaceutical chemistry -- Periodicals; 615.19005
• DOI: 10.1002/cmdc.201300479
• Languages: English
• ISSNs: 1860-7179

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>Iridium(III) complexes of the type [Ir(η<sup>5</sup>‐C<sub>5</sub>Me<sub>5</sub>)Cl<sub>2</sub>{Ph<sub>2</sub>PCH<sub>2</sub>CH<sub>2</sub>CH<sub>2</sub>S(O)<sub><italic>x</italic></sub>Ph‐κ<italic>P</italic>}] (<italic>x</italic>=0–2; <bold>1</bold>–<bold>3</bold>) and [Ir(η<sup>5</sup>‐C<sub>5</sub>Me<sub>5</sub>)Cl{Ph<sub>2</sub>PCH<sub>2</sub>CH<sub>2</sub>CH<sub>2</sub>S(O)<sub><italic>x</italic></sub>Ph‐κ<italic>P</italic>, κ<italic>S</italic>}][PF<sub>6</sub>] (<italic>x</italic>=0–1; <bold>4</bold> and <bold>5</bold>) with 3‐(diphenylphosphino)propyl phenyl sulfide, sulfoxide, and sulfone ligands Ph<sub>2</sub>PCH<sub>2</sub>CH<sub>2</sub>CH<sub>2</sub>S(O)<sub><italic>x</italic></sub>Ph were designed, synthesized, and characterized fully, including X‐ray diffraction analyses for complexes <bold>3</bold> and <bold>4</bold>. In vitro studies against human thyroid carcinoma (8505C), submandibular carcinoma (A253), breast adenocarcinoma (MCF‐7), colon adenocarcinoma (SW480), and melanoma (518A2) cell lines provided evidence for the high biological potential of the neutral and cationic iridium(III) complexes. Neutral iridium(III) complex <bold>5</bold> proved to be the most active, with IC<sub>50</sub> values up to about 0.1 μ<sc>M</sc>, 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 <bold>5</bold> exerts its tumoricidal action. The described iridium(III) complexes represent potential leads in the search for novel metal‐based anticancer agents.</p> </abstract>