Non-Flat Bisbenzylisoquinoline Alkaloid Fangchinoline As a Class of Potent G-Quadruplex Stabilizer with Anti-cancer Activity  

作　　者：Qian Li Junfeng Xiang Yalin Tang 

机构地区：[1]Beijing National Laboratory for Molecular Sciences (BNLMS), Center for Molecular Sciences,State Key Laboratory for Structural Chemistry of Unstable and Stable Species, Institute of Chemistry, Chinese Aeademy of Sciences, Beijing 100190, China

出　　处：《Chinese Journal of Chemistry》2015年第9期1041-1048,共8页中国化学（英文版）

基　　金：We thank the National Natural Science Foundation of China （Nos. 21472197, 91027033, 81072576, 21205121, 21305145 and 31200576）, the Major National Basic Research Projects （973） （No. 2013CB733701）, the ＂Strategic Priority Research Program＂ of the Chinese Academy of Sciences （No. XDA09030307）, and the Key Program of the Chinese Academy of Sciences （No. KJCX2-EW-N06-01）.

摘　　要：Compounds selectively binding and stabilizing G-quadruplex structures could inhibit the telomerase or down- regulate the oncogenes and may act as anti-cancer drugs. An alkaloid with non-flat structure, fangchinoline, showed to strongly stabilize the intermolecular and intramolecular parallel stranded G-quadruplex structure, increasing melting temperature by 20 and 23℃, respectively. The binding mode was investigated by using NMR and molec- ular modelling methods. Four human cell lines （HL-60, BGC-823, Be1-7402 and KB） were taken to test the an- ti-proliferation effects of fangchinoline and the IC50 values were ranged from 16 to 32 μmol/L. These results showed that the fangchinoline or related moiety derivatives may represent a class of telomere-targeted agents as po- tential anti-cancer drugs.Compounds selectively binding and stabilizing G-quadruplex structures could inhibit the telomerase or down- regulate the oncogenes and may act as anti-cancer drugs. An alkaloid with non-flat structure, fangchinoline, showed to strongly stabilize the intermolecular and intramolecular parallel stranded G-quadruplex structure, increasing melting temperature by 20 and 23℃, respectively. The binding mode was investigated by using NMR and molec- ular modelling methods. Four human cell lines （HL-60, BGC-823, Be1-7402 and KB） were taken to test the an- ti-proliferation effects of fangchinoline and the IC50 values were ranged from 16 to 32 μmol/L. These results showed that the fangchinoline or related moiety derivatives may represent a class of telomere-targeted agents as po- tential anti-cancer drugs.

关 键 词：G-QUADRUPLEX alkaloid non-flat anti-cancer drug 

分 类 号：TQ463.5[化学工程—制药化工] O629.3[理学—有机化学]