Habala Ladislav, Galanski Mathea S., Yasemi Afshin, Nazarov Alexey A, von Keyserlingk Nikolai Graf, Keppler Bernhard K
Institute of Inorganic Chemistry -- Bioinorganic, Environmental- and Radiochemistry, University of Vienna, Waehringerstr. 42, A-1090 Vienna, Austria.
Eur J Med Chem. 2005 Nov;40(11):1149-55. doi: 10.1016/j.ejmech.2005.06.003. Epub 2005 Jul 22.
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.
为了改善抗癌药物奥沙利铂（反式 - R，R - 环己烷 - 1,2 - 二胺）草酸铂（II）的药理学特性，并探索活性 - 结构关系，已合成了新的单烷基和二烷基取代的奥沙利铂类似物。遵循一种新的合成策略，可以制备在环己烷环的1、2、4和5碳原子处具有确定立体化学的外消旋体，这是可靠的构效关系和后续对映体拆分的基础。在九种肿瘤细胞系中评估了细胞毒性，结果表明庞大的取代基对奥沙利铂衍生物的细胞毒性效力有负面影响。就抗增殖特性而言，4 - 甲基 - 、顺式 - 4,5 - 二甲基 - ，尤其是4,4 - 二甲基 - 反式 - 环己烷 - 1,2 - 二胺（草酸根）铂（II）配合物是最有希望进一步评估的候选物。
