title: Synthesis and structure-activity relationships of mono- and dialkyl-substituted oxaliplatin derivatives.
abstract: In order to improve the pharmacological profile of the anticancer drug oxaliplatin, (trans-R,R-cyclohexane-1,2-diamine)oxalatoplatinum(II), and to explore activity-structure relationships, new mono- and dialkyl substituted oxaliplatin analogues have been synthesized. Following a new synthetic strategy, racemates with a defined stereochemistry at carbon atoms 1, 2, 4, and 5 of the cyclohexane ring could be prepared, which are the bases for reliable structure-activity relationships and the following enantiomer resolution. The cytotoxicity was evaluated in nine tumor cell lines, indicating that bulky substituents have a negative influence on the cytotoxic potency of the oxaliplatin derivatives. With respect to the antiproliferative properties, the 4-methyl-, cis-4,5-dimethyl-, and especially the 4,4-dimethyl-trans-cyclohexane-1,2-diamine(oxalato)platinum(II) complexes are the most promising candidates to be further evaluated.
authors.affiliation: Institute of Inorganic Chemistry -- Bioinorganic, Environmental- and Radiochemistry, University of Vienna, Waehringerstr. 42, A-1090 Vienna, Austria.
authors.forename: Ladislav
authors.initials: L
authors.lastname: Habala
authors.forename: Mathea S.
authors.initials: MS
authors.lastname: Galanski
authors.forename: Afshin
authors.initials: A
authors.lastname: Yasemi
authors.forename: Alexey A
authors.initials: AA
authors.lastname: Nazarov
authors.forename: Nikolai Graf
authors.initials: NG
authors.lastname: von Keyserlingk
authors.forename: Bernhard K
authors.initials: BK
authors.lastname: Keppler
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D003510:Cyclohexanes / Q000138:chemical synthesis / Q000737:chemistry; D003959:Diamines / Q000138:chemical synthesis / Q000737:chemistry; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D009944:Organoplatinum Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000077150:Oxaliplatin; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D003510:Cyclohexanes; D003959:Diamines; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin