摘要
目的:合成木犀草素Mannich碱衍生物并考察其抗癌活性。方法:室温下木犀草素与甲醛、胺经Mannich反应得到8种Mannich碱衍生物。采用MTT法,以5氟-尿嘧啶(5-Fu)为阳性对照药,通过人宫颈癌细胞(Hela)、人胃癌细胞(SGC-7901)、人结肠癌细胞(HCT-116)、人白血病细胞(K562)、人乳腺癌细胞(MCF-7)、人前列腺癌细胞(DU-145)等6种肿瘤细胞进行体外抗癌活性评价,以正常人胚肾上皮细胞(HEK-293)为毒性对照;对化合物8h进行抗癌分子机制研究。结果:合成的8种化合物结构经1H-NMR、13C-NMR和MS确证。体外抗癌活性试验表明部分化合物显示出比木犀草素更好的抗癌活性。结论:化合物8h可能通过线粒体途径抑制SGC-7901细胞增殖,从而诱导细胞凋亡。
Objective：To synthesize Mannich base derivatives of luteolin and investigate their antitumor activities in vitro.Methods： Luteolin was reacted with formaldehyde and amines to form 8 Mannich base derivatives at room temperature.Taking fluorouracil as control,their antitumor activities were evaluated in vitro using MTT assay in the human cervical carcinoma cell line（Hela）,human gastric cancer cell line（SGC-7901）,human colon cancer cell line（HCT-116）,human leukemia cell line（K562）,human breast adenocarcinoma cell line（MCF-7）,and human prostate carcinoma cells（DU-145）.Human embryonic kidney 293（HEK-293） cells were used as the model cell for assaying cytotoxicity.For compound 8h,the molecular mechanism of its antitumor action was examined.Results： The structures of 8 compounds were characterized by 1H-NMR,13C-NMR and MS.The antitumor tests indicated that the activities of several compounds were superior to that of luteolin.Conclusion： Compound 8h can induce apoptosis of SGC-7901 cells,which is possibly mediated by the mitochondria-dependent pathway.
出处
《中国新药杂志》
CAS
CSCD
北大核心
2011年第8期743-747,共5页
Chinese Journal of New Drugs
基金
江苏省自然科学基金企业博士创新项目(BK2009549)
常州大学校引进基金(ZMF07020020)
