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Design and Synthesis of Tetrandrine Derivatives as Potential Anti‐tumor Agents Against A549 Cell Lines
Author(s) -
Niu Nana,
Jin Tao,
Li Xia,
Xu Jinfang,
Qu Tingli,
Bodwell Graham J.,
Zhao Zhengbao
Publication year - 2019
Publication title -
chemistryselect
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.437
H-Index - 34
ISSN - 2365-6549
DOI - 10.1002/slct.201803592
Subject(s) - tetrandrine , chemistry , a549 cell , apoptosis , cell culture , sonogashira coupling , in vitro , western blot , stereochemistry , pharmacology , biochemistry , biology , palladium , genetics , gene , catalysis
Tetrandrine ( 1 ) was converted to 5‐bromotetrandrine ( 2 ) using a mild oxidative system (DMSO/HBr). Suzuki‐Miyaura and Sonogashira cross‐coupling reactions were then employed to yield a set of 5‐substituted tetrandrine derivatives. A total of 19 new compounds was synthesized and they were characterized by 1 H NMR, 13 C NMR and HRMS. Their antiproliferative activities against A549 cell lines in vitro were evaluated using the MTT assay. Most of the compounds were found to possess significant inhibitory activities and compound 7 had the highest (IC 50 = 3.04 μM). Further studies on the mechanism demonstrated by compound 7 showed that it promotes apoptosis of A549 cells in a dose‐dependent manner and reduces the mitochondrial membrane potential. Western blot results showed that the compound up‐regulated the levels of Bax protein and down‐regulated the level of Bcl‐2 protein. Compared to the control group, the expression of cleaved‐caspase 3 and cleaved‐PARP in cells was significantly increased.