Highly active neutral ruthenium(II) arene complexes: synthesis, characterization, and investigation of their anticancer properties.
Reactions of ω-diphenylphosphino-functionalized alkyl phenyl sulfides Ph(2)P(CH(2))(n)SPh (n=1, L1; 2, L2; 3, L3), sulfoxides Ph(2)P(CH(2))(n)S(O)Ph (n=1, L4; 2, L5; 3, L6) and sulfones Ph(2)P(CH(2))(n)S(O)(2)Ph (n=1, L7; 2, L8; 3, L9) with the dinuclear chlorido bridged ruthenium(II) complex [{Ru(η(6)-p-cymene)Cl(2)}(2)] afforded mononuclear ruthenium(II) complexes of the type [Ru(η(6)-p-cymene)Cl(2){Ph(2)P(CH(2))(n)S(O)(x)Ph-κP}] (n/x=1/0, 1; 2/0, 2; 3/0, 3; 1/1, 4; 2/1, 5; 3/1, 6; 1/2, 7; 2/2, 8; 3/2, 9) having the P(∩)S(O)(x) ligands κP coordinated. The complexes were characterized by (1)H, (13)C and (31)P NMR spectroscopy. The crystal structures of complexes 2, 7·CH(2)Cl(2) and 8 were determined by X-ray diffraction analysis. All complexes have been screened for cytostatic activity against cell lines 518A2, 8505C, A253, MCF-7, and SW480. In vitro biological experiments demonstrate that these compounds are active toward the used cell lines. The ruthenium(II) complex [Ru(η(6)-p-cymene)Cl(2){Ph(2)P(CH(2))(2)SPh-κP}] (2) is the most active compound in the human cancer cell line MCF-7 with the IC(50) value 1.4 μM lower than cisplatin (2.0 μM).
Institute of Chemistry, Martin Luther University of Halle-Wittenberg, Kurt-Mothes-Strasse 2, D-06120 Halle, Germany.
Gerd
G
Ludwig
Goran N
GN
Kaluđerović
Martin
M
Bette
Michael
M
Block
Reinhard
R
Paschke
Dirk
D
Steinborn
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D056831:Coordination Complexes / Q000138:chemical synthesis* / Q000494:pharmacology; D000081007:Cymenes; D006801:Humans; D020128:Inhibitory Concentration 50; D009682:Magnetic Resonance Spectroscopy; D039821:Monoterpenes / Q000737:chemistry*; D012428:Ruthenium / Q000737:chemistry*; D013329:Structure-Activity Relationship; D013440:Sulfides / Q000737:chemistry*; D013450:Sulfones / Q000737:chemistry*; D013454:Sulfoxides / Q000737:chemistry*; D014961:X-Ray Diffraction
D000970:Antineoplastic Agents; D056831:Coordination Complexes; D000081007:Cymenes; D039821:Monoterpenes; D013440:Sulfides; D013450:Sulfones; D013454:Sulfoxides; C007210:4-cymene; D012428:Ruthenium; D002945:Cisplatin