Non-Flat Bisbenzylisoquinoline Alkaloid Fangchinoline As a Class of Potent G-Quadruplex Stabilizer with Anti-cancer Activity
Qian Li
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 Academy of Sciences, Beijing 100190, China
Search for more papers by this authorJunfeng Xiang
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 Academy of Sciences, Beijing 100190, China
Search for more papers by this authorCorresponding Author
Yalin Tang
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 Academy of Sciences, Beijing 100190, China
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 Academy of Sciences, Beijing 100190, China, Tel.: 0086-010-62522090; Fax: 0086-010-62522090Search for more papers by this authorQian Li
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 Academy of Sciences, Beijing 100190, China
Search for more papers by this authorJunfeng Xiang
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 Academy of Sciences, Beijing 100190, China
Search for more papers by this authorCorresponding Author
Yalin Tang
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 Academy of Sciences, Beijing 100190, China
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 Academy of Sciences, Beijing 100190, China, Tel.: 0086-010-62522090; Fax: 0086-010-62522090Search for more papers by this authorAbstract
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°C, respectively. The binding mode was investigated by using NMR and molecular modelling methods. Four human cell lines (HL-60, BGC-823, Bel-7402 and KB) were taken to test the anti-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 potential anti-cancer drugs.
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