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目的设计并合成一系列取代苯基亚甲基环戊酮衍生物,对它们的体外抗肿瘤活性进行初步筛选并探讨其构效关系。方法使用化学方法对目标化合物进行合成,采用MTT法测定目标化合物的体外抗肿瘤活性,利用CoMFA法讨论构效关系。结果与结论合成了23个目标化合物,其中22个未见文献报道,目标化合物的结构经元素分析、1H-NMR和MS谱确认。体外抗肿瘤活性初筛结果显示,化合物Ⅰa和Ⅰb对Bel-7402、HCT-8、A-549肿瘤细胞均表现出较高的细胞毒性,化合物Ⅱg对Bel-7402和HCT-8呈现选择性抑制,但对A-549无抑制作用,化合物Ⅲa～Ⅲf对3种肿瘤细胞均无明显抑制作用。CoMFA结果显示,5位芳基胺甲基结构中,胺基的对位含有空间位阻较小和吸电子基团时将有助于提高化合物的活性,而胺基的邻位和间位连有空间位阻较大和供电子基团将会增强化合物的活性。
OBJECTIVE To design and synthesize a series of substituted phenylmethylcyclopentanone derivatives to screen their anti-tumor activity in vitro and to explore their structure-activity relationship. Methods The target compounds were synthesized by chemical methods. The antitumor activity of the target compounds was determined by MTT assay. The structure-activity relationship was discussed by CoMFA assay. RESULTS AND CONCLUSIONS Totally 23 target compounds were synthesized, of which 22 were not reported in the literature. The structures of target compounds were confirmed by elemental analysis, 1H-NMR and MS spectra. The results of in vitro antitumor activity showed that compounds Ⅰa and Ⅰb showed higher cytotoxicity on Bel-7402, HCT-8 and A-549 tumor cells, and compound Ⅱg selectively inhibited Bel-7402 and HCT-8 , But had no inhibitory effect on A-549. The compounds Ⅲa ~ Ⅲf had no obvious inhibitory effect on the three kinds of tumor cells. The results of CoMFA showed that the amino group in the 5-arylaminomethyl structure contains steric hindrance and the electron-withdrawing group will help to improve the activity of the compound. However, the ortho- and meta- There is steric hindrance and electron donating groups will enhance the activity of the compounds.