摘要
目的:合成鞣花鞣质肠道代谢产物尿石素(urolithins)系列物,并研究其体外抗癌活性。方法:本研究通过溴化反应、醛基氧化反应、铜催化的偶联酯化反应以及去甲基化反应等有机化学反应,构建了5种urolithins的合成路线,并利用核磁共振氢谱、碳谱确证了其结构。随后采用CCK8法测定了所得化合物对膀胱癌T24细胞增殖的影响。结果:显示urolithin A,urolithin B,甲基化urolithin C及甲基化urolithin A均可不同程度的抑制膀胱癌T24细胞增殖,其IC50分别为87.59,36.08,46.65,和213.97μmol·L-1。其中urolithin B对T24细胞的增殖抑制活性最强,urolithin C对T24细胞几乎没有抑制作用。结论:本研究合成的5种urolithins除urolithin C以外对T24细胞均有不同程度的抑制作用,且urolithin B对T24细胞的抑制作用最强。该合成路线简单、反应条件温和,同时为尿石素及其衍生物的合成和设计提供了新的思路。
OBJECTIVE To synthesize the urolithins of metabolites of ellagitannins produced by the bacterias in the intestine, and to study their anti-cancer activity in vitro. METHODS In this study, five synthetic routes of urolithins were constructed by organic chemical reactions such as bromination reaction, aldehyde oxidation reaction, copper-catalyzed coupling esterification reaction, and demethylation reaction, and their structures were confirmed by nuclear magnetic resonance hydrogen spectroscopy and carbon spectroscopy. The effect of the resulting compounds on bladder cancer T24 cell proliferation was subsequently determined using the CCK8 assay.RESULTS Urolithin A, urolithin B, methylated urolithin C and methylated urolithin A could inhibit the proliferation of bladder cancer T24 cells to different extents, with IC50 of 87.59, 36.08, 46.65, and 213.97 μmol·L-1, respectively. Among them, urolithin B had the strongest proliferative inhibitory activity on T24 cells, and urolithin C had little inhibitory effect on T24 cells. CONCLUSION The five urolithins synthesized in this study have different inhibitory effects on T24 cells except urolithin C, and urolithin B has the strongest inhibitory effect on T24 cells. The synthetic route is simple and the reaction conditions are mild, and it also provides a new idea for the synthesis and design of urolithiasis and its derivatives.
作者
周本宏
韦平
兰昱
张孟科
ZHOU Ben-hong;WEI Ping;LAN Yu;ZHANG Meng-ke(Department of Pharmacy,Wuhan University,Renmin Hospital,Hubei Wuhan 430060,China;School of Pharmaceutical Sciences,Wuhan University,Hubei Wuhan 430071,China)
出处
《中国医院药学杂志》
CAS
北大核心
2020年第5期528-532,共5页
Chinese Journal of Hospital Pharmacy
基金
国家自然科学基金资助项目(编号:31770381)。
关键词
鞣花鞣质
尿石素
合成
抗膀胱癌
ellagitannins
urolithins
synthesis
anti-bladder cancer
作者简介
周本宏,男,博士,教授,研究方向:中药天然药物活性成分及临床代谢药理学研究,电话:15335898431,E-mail:benhongzh@whu.edu.cn。
