哌啶酮类法尼基转移酶抑制药的微波幅射合成与抗肿瘤活性

目的合成设计哌啶酮类法尼基转移酶抑制药，并对其抗肿瘤活性进行初步评价。方法以取代苯甲醛为起始原料，经Perkin反应和Michael加成，最后在微波辐射条件下环合得到目标化合物，并用MTT法测试它们抑制人Hela细胞和ANC-1细胞的IC50值。结果采用微波辐射技术合成哌啶酮类化合物，反应时间为20～45 min，产率为36.0%～67.1%。经1H-NMR、ESI-MS及IR对化合物的结构确证，总共合成11个新化合物。初步抗肿瘤活性测试结果显示11个目标化合物均有抑瘤活性，其中8个化合物IC50值低于氟尿嘧啶。结论哌啶酮类法尼基转移酶抑制药的合成路线可靠，具有显著抗肿瘤活性。

Synthesis and Antitumor Activities of Piperidone Farnesyltransferase Inhibitors

Objective To synthesize the piperidone farnesyltransferase inhibitors under microwave irradiation and to observe their antitumor activities in vitro. Methods Under microwave irradiation condition, the target compounds were synthesized by cyclization reaction from the substance which was synthesized from 2-substituted benzaldehyde by the Perkin reaction and Michael addition. The IC_ 50 values of antitumor activities to human Hela cell and ANC-1 cell were tested by MTT method. Results The target compounds under microwave irradiation were obtained within 20-45 min. The average production rate were 36.0%-67.1%. Eleven new compounds were identified by IR, 1H-NMR and ESI-MS, and all of them showed antitumor activities in preliminary experiments. IC_ 50 values of eight compounds were below that of 5-Fu. Conclusion The synthesis method of piperidone farnesyltransferase inhibitors is reliable. And piperidone farnesyltransferase inhibitors have certain antitumor activities.