title: Synthesis and antitumor activity of 1,2-diaminocyclohexane platinum(IV) complexes.
abstract: The synthesis, characterization, and antitumor activity of a series of platinum(IV) complexes of the type DACH-PtIV(X)2Y (where DACH = trans-dl, or trans-l-1,2-diaminocyclohexane, X = OH or Cl, and Y = oxalato, malonato, methylmalonato, tartronato, ketomalonato, 1,1-cyclopropanedicarboxylato, or 1,1-cyclobutanedicarboxylato, are described. These complexes have been characterized by elemental analysis, HPLC, and infrared and 195Pt NMR spectroscopic techniques. The complexes had good in vitro cytotoxic activity (IC50 = 0.14-7.6 micrograms/ml) and were highly active in vivo against leukemia L1210 cells (%T/C = 152- > 600, cisplatin = 218). In addition, excellent in vivo antitumor activities against B16 melanoma (%T/C = 309), M5076 reticulosarcoma (100% cures) and cisplatin-resistant L1210/DDP (%T/C = 217) cell lines were also exhibited by an analog selected for further evaluation.
authors.affiliation: Department of Clinical Investigation, University of Texas M.D. Anderson Cancer Center, Houston 77030.
authors.forename: A R
authors.initials: AR
authors.lastname: Khokhar
authors.forename: S
authors.initials: S
authors.lastname: al-Baker
authors.forename: Z H
authors.initials: ZH
authors.lastname: Siddik
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000627:therapeutic use / Q000633:toxicity; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000633:toxicity; D004351:Drug Resistance; D007202:Indicators and Reagents; D007939:Leukemia L1210 / Q000188:drug therapy; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008546:Melanoma, Experimental / Q000188:drug therapy; D051379:Mice; D008815:Mice, Inbred Strains; D009944:Organoplatinum Compounds / Q000138:chemical synthesis* / Q000627:therapeutic use / Q000633:toxicity; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D007202:Indicators and Reagents; D009944:Organoplatinum Compounds; D002945:Cisplatin