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Non‐Flat Bisbenzylisoquinoline Alkaloid Fangchinoline As a Class of Potent G‐Quadruplex Stabilizer with Anti‐cancer Activity
Author(s) -
Li Qian,
Xiang Junfeng,
Tang Yalin
Publication year - 2015
Publication title -
chinese journal of chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.28
H-Index - 41
eISSN - 1614-7065
pISSN - 1001-604X
DOI - 10.1002/cjoc.201400841
Subject(s) - chemistry , alkaloid , stereochemistry , moiety , g quadruplex , telomere , telomerase , intramolecular force , two dimensional nuclear magnetic resonance spectroscopy , biochemistry , dna , gene
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 IC 50 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.