Synthesis and Biological Activities of (R)- and (S)-N-(4-Methoxyphenyl)-N,2,6-trimethyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-aminium Chloride as Potent Cytotoxic Antitubulin Agents
Synthesis and Biological Activities of (R)- and (S)-N-(4-Methoxyphenyl)-N,2,6-trimethyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-aminium Chloride as Potent Cytotoxic Antitubulin Agents
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DOI：
10.1021/jm2007722
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发表时间：
2011-09-08
影响因子：
7.3
通讯作者：
Mooberry, Susan L.
中科院分区：
文献类型：
--
作者：
Ganglee, Aleem;Zhao, Ying;Mooberry, Susan L.
（R，S）-1是一种有效的抗有丝分裂化合物。(R)-1以（R）-和（S）-3-甲基己二酸为原料合成了中心点HCl和（S）-1中心点HCl。这两种对映体都是细胞增殖的有效抑制剂，并引起细胞微管丢失和有丝分裂停滞。它们抑制纯化的微管蛋白组装和[H-3]秋水仙碱与微管蛋白的结合，其中（S）-1的效力约为2倍。然而，对60种肿瘤细胞系的细胞毒性表明，（S）-异构体的效力是（R）-异构体的10至88倍。
(R,S)-1 is a potent antimitotic compound. (R)-1 center dot HCl and (S)-1 center dot HCl were synthesized from (R)- and (S)-3-methyladipic acid. Both enantiomers were potent inhibitors of cell proliferation and caused cellular microtubule loss and mitotic arrest. They inhibited purified tubulin assembly and the binding of [H-3]colchicine to tubulin, with (S)-1 being about twice as potent. Cytotoxicity against 60 tumor cell lines, however, indicated that the (S)-isomer was 10- to 88-fold more potent than the (R)-isomer.