Chinese Journal of Organic Chemistry >
Synthesis and in Vitro Antitumor Activity of Matrine Semicarbazide Derivatives
Received date: 2022-09-30
Revised date: 2022-12-11
Online published: 2023-01-12
Supported by
National Innovation and Entrepreneurship Training Program for College Students(202010601021); Guangxi Young and Middle-Aged Scientific Research Basic Ability Improvement Project for Colleges and Universities(2019KY051); Natural Science Foundation of Guangxi Province(2018GXNSFAA281200); Project for Science Research and Technology Development of Guilin City(20210227-1)
In order to search for novel antitumor drugs with high efficiency and low toxicity, matrine semicarbazide derivatives were designed and synthesized. The antiproliferative activities of target compounds in four human cancer cell lines of A549 (lung), HepG2 (liver), Hela (epithelial cervical), MGC-803 (gastric) and a human normal cell of L-O2 (liver) were evaluated by methyl thiazolyl tetrazolium (MTT) assay. Biological screening results demonstrated that most of the derivatives exhibited more potent cytotoxicity against tumor cell lines superior to parent compound matrine. Among them, compounds of 14-formyl-15-chloro-matrine N-(3-chlorophenyl) semicarbazide (6c) and 14-formyl-15-chloro-matrine N-(3-nitrophenyl) semicarbazide (6f) displayed better antiproliferative activity with IC50 values of (11.70±0.25) and (15.61±0.07) μmol/L toward A549 cells compared with camptothecin, and with IC50 values of (11.32±1.07) and (9.27±2.03) μmol/L against MGC-803 cells. Moreover, they exhibited lower cytotoxicity against human normal liver cell line L-O2. Flow cytometry and JC-1 mitochondrial membrane potential detection showed that compound 6f could induce apoptosis of MGC803 cells and reduce the mitochondrial membrane potential. It would provide a new idea for the structural modification of matrine.
Key words： matrine; semicarbazide; synthesis; in vitro antitumor activity
Panxing Pang , Rong Ning , Chuang Zhu , Wenjie Huang , Xianli Ma , Caina Jiang , Fangyao Li , Xiaoqun Zhou . Synthesis and in Vitro Antitumor Activity of Matrine Semicarbazide Derivatives[J]. Chinese Journal of Organic Chemistry, 2023 , 43(6) : 2126 -2135 . DOI: 10.6023/cjoc202209040
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