Cytotoxic Rhodium(III) and Iridium(III) Polypyridyl Complexes: Structure–Activity Relationships, Antileukemic Activity, and Apoptosis Induction

Whereas the cytostatic agents mer‐[RhX3(DMSO)(pp)] (X=Cl, Br; pp=phen, dpq) are considerably more potent than their facial isomers, this order is reversed for the analogous kinetically more inert IrIII polypyridyl complexes. The complexes induce specific apoptotic cell death in leukemia and lymphoma cells via the intrinsic mitochondrial pathway and cause negligible necrotic damage.

[1]  A. Zajdel,et al.  Synthesis, structure and antitumor activity of [RhCl3(N-N)(DMSO)] polypyridyl complexes. , 2008, Journal of inorganic biochemistry.

[2]  R. Gust,et al.  Synthesis, cellular uptake and structure-activity relationships for potent cytotoxic trichloridoiridium(III) polypyridyl complexes. , 2008, Journal of inorganic biochemistry.

[3]  R. Gust,et al.  Cytotoxic half-sandwich rhodium(III) complexes: Polypyridyl ligand influence on their DNA binding properties and cellular uptake , 2008 .

[4]  S. Wölfl,et al.  Synthesis, biological activity, and structure-activity relationships for potent cytotoxic rhodium(III) polypyridyl complexes. , 2008, Journal of medicinal chemistry.

[5]  Wen-jie Zheng,et al.  Differences in structure, physiological stability, electrochemistry, cytotoxicity, DNA and protein binding properties between two Ru(III) complexes. , 2008, Journal of inorganic biochemistry.

[6]  R. Gust,et al.  Influence of the Polypyridyl (pp) Ligand Size on the DNA Binding Properties, Cytotoxicity and Cellular Uptake of Organoruthenium(II) Complexes of the Type [(η6‐C6Me6)Ru(L)(pp)]n+ [L = Cl, n = 1; L = (NH2)2CS, n = 2] , 2007 .

[7]  M. Taschner,et al.  Ovarian cancer activity of cyclic amine and thiaether metal complexes. , 2007, Journal of medicinal chemistry.

[8]  W. Sheldrick,et al.  Coligand tuning of the DNA binding properties of half-sandwich organometallic intercalators : Influence of polypyridyl (pp) and monodentate ligands (L = Cl, (NH2)2CS, (NMe2)2CS) on the intercalation of (η5 -pentamethylcyclopentadienyl )-iridium(iii)-dipyridoquinoxaline and -dipyridophenazine complex , 2007 .

[9]  C. Turro,et al.  Dirhodium(II,II) complexes: molecular characteristics that affect in vitro activity. , 2006, Journal of medicinal chemistry.

[10]  Erwin P. L. van der Geer,et al.  Controlling ligand substitution reactions of organometallic complexes: tuning cancer cell cytotoxicity. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[11]  G. Henze,et al.  Synthesis of Demethylxanthohumol, a New Potent Apoptosis‐Inducing Agent from Hops , 2005, Chemistry & biodiversity.

[12]  R. Gust,et al.  Antitumor-active cobalt-alkyne complexes derived from acetylsalicylic acid: studies on the mode of drug action. , 2005, Journal of medicinal chemistry.

[13]  N. Katsaros,et al.  Rhodium and its compounds as potential agents in cancer treatment. , 2002, Critical reviews in oncology/hematology.

[14]  J. Zakrzewska‐Czerwińska,et al.  Rhodium(III) complexes with polypyridyls and pyrazole and their antitumor activity , 2002 .

[15]  B. Dörken,et al.  Piceatannol, a hydroxylated analog of the chemopreventive agent resveratrol, is a potent inducer of apoptosis in the lymphoma cell line BJAB and in primary, leukemic lymphoblasts , 2001, Leukemia.

[16]  R. Eldik,et al.  Kinetics and Mechanism of Water Substitution at Half‐Sandwich Iridium(III) Aqua Cations Cp*Ir(A−B)(H2O)2+/+ in Aqueous Solution (Cp* = η5‐Pentamethylcyclopentadienyl Anion; A−B = Bidentate N,N or N,O Ligand) , 2001 .

[17]  B. Dörken,et al.  Activation of caspase-8 in drug-induced apoptosis of B-lymphoid cells , 2001 .

[18]  J. Collins,et al.  A 1H NMR Study of the DNA Binding of Ruthenium(II) Polypyridyl Complexes , 1998 .

[19]  A. Bergamo,et al.  Rhodium(III) analogues of antitumour-active ruthenium(III) compounds: The crystal structure of [ImH][trans-RhCl4(Im)2] (Im=imidazole) , 1998 .

[20]  T. Wieder,et al.  Induction of Ceramide-mediated Apoptosis by the Anticancer Phospholipid Analog, Hexadecylphosphocholine* , 1998, The Journal of Biological Chemistry.

[21]  A Orfao,et al.  Proposals for the immunological classification of acute leukemias. European Group for the Immunological Characterization of Leukemias (EGIL). , 1995, Leukemia.

[22]  E. Alessio,et al.  A new linkage isomer of RhCl3(DMSO)3: photochemical synthesis, crystal structure and reactivity of mer,trans-RhCl3(DMSO)2(DMSO). , 1993 .

[23]  R. Morris,et al.  Sulfur-bonded sulfoxide complexes of rhodium(III) and rhodium(I) , 1980 .

[24]  J. Broomhead,et al.  Iridium(III) and rhodium(III) mono-and bis(1,10-phenanthroline) complexes and the optical isomers of iridium(III), rhodium(III), chromium(III), and cobalt(III) dihalobis(1-10-phenanthroline) complex cations , 1971 .

[25]  E. Mckenzie,et al.  Rhodium(III) compounds with 1,10-phenanthroline and 2,2′-bipyridyl , 1970 .