尿石素B衍生物合成及抗膀胱癌T24细胞增殖活性  

Synthesis of urolithin B derivatives and their anti-proliferation activity on bladder cancer T24cells

作　　者：田弥 周本宏[1,2] 兰昱 卢笛笙 TIAN Mi;ZHOU Ben-hong;LAN Yu;LU Di-sheng(Depaetment of Pharmacy,Wuhan University,Renmin Hospital,Hubei Wuhan 430060,China;School of Pharmaceutical Sciences,Wuhan University,Hubei Wuhan 430072,China)

机构地区：[1]武汉大学人民医院药学部,湖北武汉430060 [2]武汉大学药学院,湖北武汉430072

出　　处：《中国医院药学杂志》2023年第10期1066-1070,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)。

摘　　要：目的:利用拼合原理合成一系列尿石素B衍生物并探究其对人膀胱癌T24细胞的抗增殖活性。方法:通过烷基化反应,以尿石素B为母核,环状胺基结构(吡咯烷、N-甲基哌嗪、4-甲基哌啶、吗啡啉)为末端,1,3-二溴丙烷作为连接两者的柔性碳链,合成一系列尿石素B衍生物。同时利用CCK-8实验测定尿石素B衍生物和阳性药5-氟尿嘧啶对人膀胱癌T24细胞的抗增殖活性。结果:成功合成了4种尿石素B衍生物;在CCK-8实验中,UB1和UB2作用不同时间的IC50都大于150μmol·L^(-1),对T24细胞增殖抑制作用较小;UB3与5-氟尿嘧啶抑制T24细胞增殖的活性相当,而UB4的抑制作用更加显著,在给药24,36,48 h后测得IC50分别达到了16.95,15.51,6.34μmol·L^(-1)。结论:4种衍生物中UB3和UB4均可不同程度抑制膀胱癌T24细胞增殖,而UB4抑制T24细胞增殖活性最强。该研究为尿石素B衍生物开发成抗癌活性高、溶解性好、成药性强、结构新颖的有效药物提供了科学依据。OBJECTIVE To synthesize a series of urolithin B derivatives based on the combination principle and to explore their anti-proliferation activity on human bladder cancer T24 cells.METHODS A series of urolithin B derivatives were synthesized by alkylation with urolithin B as the parent nucleus,cyclic amino structure(pyrrolidine,N-methylpiperazine,4-methylpiperidine,morpholine)as the terminal,and 1,3-dibromopropane as the flexible carbon chain connecting them.At the same time,CCK-8 assay was used to determine the anti-proliferation activity of urolithin B derivatives and positive drug 5-fluorouracil on human bladder cancer T24 cells.RESULTS Four urolithin B derivatives were synthesized successfully.In CCK-8 assay,UB1 and UB2had little inhibitory effect on the proliferation of T24 cells,and the IC50was more than150μmol·L^(-1)in different time.The inhibitory effect of UB3and 5-fluorouracil on the proliferation of T24 cells was similar,while UB4was more significant,and the IC50was 16.95,15.51 and 6.34μmol·L^(-1)after 24,36 and 48 h administration respectively.CONCLUSION Among the four derivatives,UB3and UB4could inhibit the proliferation of bladder cancer T24 cells in various degrees,while UB4hadthe strongest inhibitory activity on T24 cell proliferation.It provides a scientific basis for developing urolithin B derivatives into effective drugs with high anticancer activity,good solubility,strong medicinal properties and novel structure.

关 键 词：尿石素B衍生物 合成 膀胱癌T24细胞 细胞增殖 

分 类 号：R914.5[医药卫生—药物化学]