| 殷昌青 詹晓平 兰岚 覃维曦 刘增路 毛振民.新型N-取代吡咯类化合物的体外抗肿瘤活性研究[J].,2014,14(28):5419-5423 |
| 新型N-取代吡咯类化合物的体外抗肿瘤活性研究 |
| The Anti-tumor Activity Research of Novel N-substitutedPyrrole Compounds in Vitro |
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| DOI： |
| 中文关键词: N- 取代吡咯 肿瘤细胞 构效关系 MTT 法 |
| 英文关键词: N-substituted pyrrole compounds Tumor cells Structure-activity relationships MTT assay |
| 基金项目:国家科技重大新药创制专项（2010ZX09401-404） |
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| 中文摘要: |
| 目的：研究37 个新型N- 取代吡咯类化合物的体外抗肿瘤活性，并探讨这些化合物的结构-活性关系。方法：运用MTT 法
来测试37 个化合物对5 种肿瘤细胞和1 种正常细胞的体外细胞增殖抑制活性。结果：化合物3f活性最高，其对MGC80-3 的IC50
值为61.29 滋M。同时成功地总结了新型N-取代吡咯化合物的构效关系：（1）对于吡咯母核的3 位，取代苯环上对位氯取代和对位
叔丁基取代化合物的抗肿瘤活性差不多，并且没有明显的规律性。（2）对于吡咯母核的4 位，取代基团的电子云密度对抗肿瘤活
性的影响也没有明显的规律。（3）对于吡咯母核的1 位，当3 位为对叔丁基苯基取代时，其整体活性顺序为：（苄基，溴乙基）>（甲
基，乙基，丙基，丁基）> 乙烯基；当3 位为对氯苯基取代时，其整体活性顺序为：（乙烯基，苄基）>（甲基，乙基，丙基，丁基）。结论：
为了得到更好的抗肿瘤活性化合物，吡咯母核的1 号位置上应该接入苄基等大空间位阻基团、容易形成氢键的基团或者不接入
任何取代基，从而为吡咯类化合物的进一步结构修饰以开发更高活性的抗肿瘤化合物提供指导。 |
| 英文摘要: |
| Objective:To investigate the anti-tumor activity of 37 novel N-substituted pyrrole compounds in vitro and explore the
structure-activity relationships of these compounds.Methods:Five kinds of tumor cells and one normal cell line are selected to explore
cell proliferation inhibitory activity in vitro by using MTT assay.Results:Compound 3f is found to be the most potent antitumor agent
and its IC50 value for MGC80-3 is 61.29 滋M. The structure-activity relationships reveal as follows: (1)For the position-3 of pyrrole
nucleus, the anti-tumor activity of p-chlorophenyl and p-tertbutylphenyl substituted compounds is similar and there is no obvious
regularity. (2) For the position-4 of pyrrole nucleus, the electron density of substitutes also has no regularity. (3) When the substitute is
p-tertbutylphenyl in the position-3, the order of substituents' overall activity in position-1 of pyrrole nucleus is (benzyl, bromine ethyl) >
(methyl, ethyl, propyl, butyl) > vinyl. When the substitute is p-chlorophenyl in the position-3, the order of substituents'overall activity in
position-1 of pyrrole nucleus is (vinyl, benzyl) > (methyl, ethyl, propyl, butyl).Conclusion:Therefore, to get compounds with better activity,
substitutes with large steric hindrance such as benzyl, easily form hydrogen bond or no substituents should be linked in position-1 of
pyrrole nucleus. And it provides a guidance for further structural modification to find better antitumor compounds. |
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