取代苯基亚甲基环戊酮衍生物的设计、合成与抗肿瘤活性  

Design,synthesis and antitumor activity of substituted benzylidenecyclopentanone derivatives

作　　者：刘鹰翔[1] 闫星[2] 孙平华[3] 马玉卓 

机构地区：[1]广州中医药大学药物化学研究室,广东广州510006 [2]广东药学院药物化学系,广东广州510006 [3]暨南大学药物化学教研室,广东广州510632

出　　处：《中国药物化学杂志》2010年第1期11-18,24,共9页Chinese Journal of Medicinal Chemistry

基　　金：广东省自然科学基金项目(994615)

摘　　要：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。Aim To design and synthesize a serial of substituted benzylidenecyclopentanone derivatives, and to determine their antitumor activities in vitro in order to discuss their structure-activity relationships. Methods The target compounds were designed and synthesized. Their antitumor activity was assayed using MTT assay in vitro. The 3D-QSAR of target compounds was studied by CoMFA. Results and conclusion Twenty-three compounds were synthesized and their chemical structures were confirmed by elemental analysis, ^1H-NMR and MS. Preliminary screening results showed that compounds Ⅰa and Ⅰb were more active to three tested tumor cell lines. Compound Ⅱ g showed selective inhibition to Bel-7402 and HCT-8 cells, and had no activity toward A-549 cell. Compounds Ⅲa - Ⅲf exhibited no obvious antitumor activity to all tested tumor cell lines. CoMFA showed that introduction of a smaller and electron-withdrawing group in 4-position of aniline would increase the antitumor activity and introduction of larger and electron-donating groups in 2- or 3-position of aniline may enhance the activity.

关 键 词：化学合成 苯基亚甲基环戊酮 抗肿瘤活性 比较分子力场分析 四氮唑盐法 

分 类 号：R914[医药卫生—药物化学]