摘要
目的研究15种番荔枝内酯类化合物对耐阿霉素乳腺癌细胞MCF-7/ADR的活性,并初步探讨其构效关系。方法MTT法检测15种番荔枝内酯化合物:annotemoyin-1(1)、annosquamin B(2)、annosquamin A(3)、annosquamin C(4)、annosquacin C(5)、urarigrandin A(6)、isodesacetyluvaricin(7)、annosquacin D(8)、annosquacin B(9)、12,15-cis-squamostatin-A(10)、squamostatin-A(11)、squamostanin-B(12)、squamostanin-A(13)、squamostatin-D(14)、squamostatin-E(15)对MCF-7/ADR细胞的抑制作用。结果所有受试化合物对MCF-7/ADR细胞均有强烈的抑制活性,且活性强于阳性药维拉帕米,化合物1的活性达到维拉帕米的190倍之多。结论四氢呋喃环与内酯环间的碳数越长,活性越强;链上羟基越多,活性越强;间双四氢呋喃型番荔枝内酯中,链上含有4个羟基的活性最强;相对构型为赤式的番荔枝内酯的活性比苏式的强,四氢呋喃环为反式构型的番荔枝内酯的活性比顺式的强。此外,相对分子质量为622,链上含有3个羟基,相对构型为赤式的邻双四氢呋喃型番荔枝内酯活性显著。
Objective To investigate the effects of 15 aunonaceous acetogenins （ACGs） on human breast cancer cell line MCF-7/ADR, and to find out their structure-activity relationship. Methods MCF-7/ADR cells were treated with 15 ACGs such as annotemoyin-1 （1）, aunosquamin B （2）, annosquamin A （3）, annosquamin C （4）, annosquacin C （5）, urarigrandin A （6）, isodesacetyluvaricin （7）, annosquacin D （8）, annosquacin B （9）, 12, 15-cis-squamostatirL-A （10）, squamostatin-A （11）, squamostanin-B （12）, squamostanin-A （13）, squamostatin-D （14）, and squamostatin-E （15） for 48 h, and the inhibition on MCF-7/ADR cells was detected using MTT assay. Results All the tested compounds showed significant inhibitory activities against MCF-7/ADR cells, and were more potent than the standard control verapamil. The activity of compound 1 was 190 times higher than that of verapamil. Conclusion The ACGs with more carbons between tetrahydrofuran （THF） ring and ？-un,;aturated lactone are more potent. If all other structural features are identical, the ACGs with more hydroxyls on aliphatic chain would be more active, and four hydroxyls might be optimal among bis-nonadjacent-THF ACGs. Moreover, ACGs with stereochemical arrangement oferythro are more active than those ofthreo, and the compounds with THF ring configuration ofcis seem to be superior to those of trans. Furthermore, bis-adjacent-THF ACGs with molecular weight of 622 and with three hydroxyl groups and stereochemical arrangement of erythro partly produce notable cytotoxicity.
出处
《中草药》
CAS
CSCD
北大核心
2014年第19期2815-2819,共5页
Chinese Traditional and Herbal Drugs
基金
国家自然科学基金资助项目(81274057
81403082)
国家教育部博士点专项基金资助项目(20113237110009)
江苏省科技厅资助项目(SBK2012853)
2012年江苏省普通高校研究生科研创新计划项目(588)
南京中医药大学青年自然科学基金(13XZR23)
关键词
番荔枝内酯
多药耐药
肿瘤
MCF-7/ADR
构效关系
annonaceous acetogenins
multidrug resistance
tumor
MCF-7/ADR
structure-activity relationships
