哌啶酮类法尼基转移酶抑制剂的设计、合成及初步抗肿瘤活性研究

利用计算机辅助药物设计软件Catalyst构建了哌啶酮类法尼基转移酶抑制剂的药效团模型, 结合所构建的药效团模型, 设计并合成出17个哌啶酮类化合物, 其中16个目标化合物未见文献报道, 其结构均经IR, MS及¹H NMR等确证. 利用MTT法得到其对于肿瘤细胞抑制的IC₅₀值. 初步生物活性测试表明, 目标化合物均具有抑瘤活性, 其中11个化合物的IC₅₀值低于阳性对照5-Fu, 并且实测值与所构建的药效团模型的预测值相关性较好.

Design, Synthesis and Antitumor Activity of Piperidone Inhibitors of Farnesyltransferase

The hypothesis of piperidone inhibitors of farnesyltransferase was built with the computer-aided drug design software--Catalyst. According to the hypothesis and structure-activity relationship of piperidone inhibitors, 17 novel piperidone inhibitors of farnesyltransferase were designed and synthesized. All compounds were characterized by IR, MS and 1H NMR. The IC50 value of the target compounds against human Hela cells was evaluated and the result showed that all compounds exhibited antitumor activity, furthermore, the IC50 value of eleven compounds was smaller than that of 5-Fu. The tested activities of the target compounds were fit to those estimated using the hypothesis that was built by Catalyst, and the excellent correlation was got.