Anticancer potential of (pentamethylcyclopentadienyl)chloridoiridium(III) complexes bearing κP and κP,κS-coordinated Ph2 PCH2 CH2 CH2 S(O)x Ph (x=0-2) ligands.
Iridium(III) complexes of the type [Ir(η(5) -C5 Me5 )Cl2 {Ph2 PCH2 CH2 CH2 S(O)x Ph-κP}] (x=0-2; 1-3) and [Ir(η(5) -C5 Me5 )Cl{Ph2 PCH2 CH2 CH2 S(O)x Ph-κP,κS}][PF6 ] (x=0-1; 4 and 5) with 3-(diphenylphosphino)propyl phenyl sulfide, sulfoxide, and sulfone ligands Ph2 PCH2 CH2 CH2 S(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 melanoma (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 μM, 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.
Institute of Chemistry, Martin Luther University Halle-Wittenberg, Kurt-Mothes-Straße 2, 06120 Halle (Germany).
Gerd
G
Ludwig
Ivan
I
Ranđelović
Danijela
D
Maksimović-Ivanić
Sanja
S
Mijatović
Mirna Z
MZ
Bulatović
Djordje
D
Miljković
Marcus
M
Korb
Heinrich
H
Lang
Dirk
D
Steinborn
Goran N
GN
Kaluđerović
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D018360:Crystallography, X-Ray; D006801:Humans; D007495:Iridium / Q000737:chemistry*; D008024:Ligands; D061986:MCF-7 Cells; D008968:Molecular Conformation; D017382:Reactive Oxygen Species / Q000378:metabolism; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D056831:Coordination Complexes; D008024:Ligands; D017382:Reactive Oxygen Species; D007495:Iridium
apoptosis; cytotoxic agents; iridium(III) complexes; metal-based drugs; sulfur-functionalized phosphorus ligands