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Synthesis, Biological Evaluation, and Docking Study of Ring‐Opening Amide Analogs of Matrine as Antitumor Agents
Author(s) -
Qian Mingcheng,
Jiang Xinyu,
Zhang Mingting,
Hu Lijuan,
Liu Huimin,
Zhao Shuai,
Zhou Xiaoying,
Chen Xin
Publication year - 2021
Publication title -
chemistry and biodiversity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.427
H-Index - 70
eISSN - 1612-1880
pISSN - 1612-1872
DOI - 10.1002/cbdv.202000979
Subject(s) - chemistry , matrine , stereochemistry , amide , hydrogen bond , docking (animal) , in vitro , in vivo , cytotoxicity , bromide , molecule , annexin , ring (chemistry) , biochemistry , organic chemistry , medicine , nursing , microbiology and biotechnology , chromatography , biology
In this article, we designed and synthesized two series of matrine analogs with ring‐opening in the lactam portion of the molecule. Our in vitro cytotoxicity study showed that analog N ‐(3‐bromophenyl)‐4‐[(1 R ,3a S ,10a R ,10b S )‐decahydro‐1 H ,4 H ‐pyrido[3,2,1‐ ij ][1,6]naphthyridin‐1‐yl]butanamide ( B11 ) with a meta ‐bromide on the phenyl ring displayed the best antiproliferative activity. Moreover, B11 induced cell cycle arrest in G1 phase and cell apoptosis in a dose‐dependent manner in A549 cells. Molecular modeling revealed that B11 achieved a higher docking score compared to its precursor tert ‐butyl (1 R ,3a S ,10a R ,10b S )‐1‐[4‐(3‐bromoanilino)‐4‐oxobutyl]octahydro‐1 H ,4 H ‐pyrido[3,2,1‐ ij ][1,6]naphthyridine‐2(3 H )‐carboxylate ( A11 , an analog of B11 with a Boc group) and parent compound matrine, possibly because B11 formed a hydrogen bond with SER91 and a halogen bond with GLN320 on the binding site of annexin A2. Overall, we discovered the potential anticancer lead compound B11 , which can be used for further study both in vitro and in vivo .