Cationic arene ruthenium(II) complexes with chelating P-functionalized alkyl phenyl sulfide and sulfoxide ligands as potent anticancer agents.

The synthesis and characterization of cationic ruthenium(II) complexes of the type [Ru(η(6)-p-cym)Cl{Ph(2)P(CH(2))(n)S(O)(x)Ph-κP,κS}][PF(6)] (n = 1-3; x = 0, 1; p-cym = p-cymene) are presented. Furthermore, their high biological potential even against cisplatin-resistant tumor cell lines and their structure-activity relationships are discussed.

[1]  R. Paschke,et al.  Highly active neutral ruthenium(II) arene complexes: synthesis, characterization, and investigation of their anticancer properties. , 2012, Journal of inorganic biochemistry.

[2]  R. Britto,et al.  Cytotoxicity of half sandwich ruthenium(II) complexes with strong hydrogen bond acceptor ligands and their mechanism of action. , 2010, Journal of inorganic biochemistry.

[3]  P. Sadler,et al.  Current applications and future potential for bioinorganic chemistry in the development of anticancer drugs. , 2009, Drug discovery today.

[4]  N. Farrell,et al.  Transferring the concept of multinuclearity to ruthenium complexes for improvement of anticancer activity. , 2009, Journal of medicinal chemistry.

[5]  Andrew D. Phillips,et al.  Influence of Structural Variation on the Anticancer Activity of RAPTA-Type Complexes: ptn versus pta , 2009 .

[6]  M. Jakupec,et al.  Water-Soluble Mixed-Ligand Ruthenium(II) and Osmium(II) Arene Complexes with High Antiproliferative Activity , 2008 .

[7]  Anna F. A. Peacock,et al.  Medicinal organometallic chemistry: designing metal arene complexes as anticancer agents. , 2008, Chemistry, an Asian journal.

[8]  Michael Groessl,et al.  In vitro anticancer activity and biologically relevant metabolization of organometallic ruthenium complexes with carbohydrate-based ligands. , 2008, Chemistry.

[9]  P. Sadler,et al.  Catalytic organometallic anticancer complexes , 2008, Proceedings of the National Academy of Sciences.

[10]  A. Spek,et al.  Ruthenium(III) chloride complex with a tridentate bis(arylimino)pyridine ligand: synthesis, spectra, X-ray structure, 9-ethylguanine binding pattern, and in vitro cytotoxicity. , 2008, Inorganic chemistry.

[11]  N. V. Stolyarova,et al.  Influence of the Spacer Length on the in Vitro Anticancer Activity of Dinuclear Ruthenium−Arene Compounds , 2008 .

[12]  P. Dyson,et al.  The "complex-in-a-complex" cations [(acac)2M subset Ru6(p-iPrC6H4Me)6(tpt)2(dhbq)3]6+: A trojan horse for cancer cells. , 2008, Angewandte Chemie.

[13]  P. Dyson,et al.  Modulation of the metastatic progression of breast cancer with an organometallic ruthenium compound. , 2008, International journal of oncology.

[14]  J. Reedijk,et al.  Synthesis, characterization and DNA binding properties of oligopyridine-ruthenium(II)-amino acid conjugates. , 2007, Journal of inorganic biochemistry.

[15]  M. Jakupec,et al.  From bench to bedside--preclinical and early clinical development of the anticancer agent indazolium trans-[tetrachlorobis(1H-indazole)ruthenate(III)] (KP1019 or FFC14A). , 2006, Journal of inorganic biochemistry.

[16]  M. Jakupec,et al.  Redox behavior of tumor-inhibiting ruthenium(III) complexes and effects of physiological reductants on their binding to GMP. , 2006, Dalton transactions.

[17]  B. Marian,et al.  KP1019 (FFC14A) from bench to bedside: preclinical and early clinical development--an overview. , 2005, International journal of clinical pharmacology and therapeutics.

[18]  M. Jakupec,et al.  Update of the preclinical situation of anticancer platinum complexes: novel design strategies and innovative analytical approaches. , 2005, Current medicinal chemistry.

[19]  P. Dyson,et al.  In vitro and in vivo evaluation of ruthenium(II)-arene PTA complexes. , 2005, Journal of medicinal chemistry.

[20]  G. Sava,et al.  Antimetastatic action and toxicity on healthy tissues of Na[trans-RuCl4(DMSO)Im] in the mouse , 1994, Clinical & Experimental Metastasis.

[21]  J. Schellens,et al.  A Phase I and Pharmacological Study with Imidazolium-trans-DMSO-imidazole-tetrachlororuthenate, a Novel Ruthenium Anticancer Agent , 2004, Clinical Cancer Research.

[22]  J. Cummings,et al.  In vitro and in vivo activity and cross resistance profiles of novel ruthenium (II) organometallic arene complexes in human ovarian cancer , 2002, British Journal of Cancer.

[23]  J. Cummings,et al.  Inhibition of cancer cell growth by ruthenium(II) arene complexes. , 2001, Journal of medicinal chemistry.

[24]  C. S. Allardyce,et al.  [Ru(η6-p-cymene)Cl2(pta)] (pta = 1,3,5-triaza-7-phosphatricyclo- [3.3.1.1]decane): a water soluble compound that exhibits pH dependent DNA binding providing selectivity for diseased cells , 2001 .

[25]  G. Sava,et al.  Blood concentration and toxicity of the antimetastasis agent NAMI-A following repeated intravenous treatment in mice. , 2000, Pharmacology & toxicology.

[26]  A. Bergamo,et al.  Ruthenium-based compounds and tumour growth control (review). , 2000, International journal of oncology.

[27]  C. Giandomenico,et al.  Current status of platinum-based antitumor drugs. , 1999, Chemical reviews.

[28]  M J Clarke,et al.  Non-platinum chemotherapeutic metallopharmaceuticals. , 1999, Chemical reviews.

[29]  P. Sadler,et al.  Metals in Medicine. , 1999, Angewandte Chemie.

[30]  G. Chu,et al.  Cellular responses to cisplatin. The roles of DNA-binding proteins and DNA repair. , 1994, The Journal of biological chemistry.

[31]  D. Scudiero,et al.  New colorimetric cytotoxicity assay for anticancer-drug screening. , 1990, Journal of the National Cancer Institute.

[32]  M. Clarke,et al.  Reduction and subsequent binding of ruthenium ions catalyzed by subcellular components. , 1980, Journal of inorganic biochemistry.

[33]  J. Trosko,et al.  Platinum Compounds: a New Class of Potent Antitumour Agents , 1969, Nature.

[34]  BARNETT ROSENBERG,et al.  Inhibition of Cell Division in Escherichia coli by Electrolysis Products from a Platinum Electrode , 1965, Nature.