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色胺水杨酸衍生物作为潜在抗肿瘤药物的设计、合成及生物学评价

Design, synthesis and biological evaluation of tryptamine salicylic acid derivatives as potential antitumor agents.

作者信息

Xiong Runde, He Dongxiu, Deng Xiangping, Liu Juan, Lei Xiaoyong, Xie Zhizhong, Cao Xuan, Chen Yanming, Peng Junmei, Tang Guotao

机构信息

Institute of Pharmacy and Pharmacology , Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study , University of South China , Hengyang , China . Email:

Jiuzhitang Co. Ltd , Changsha , China.

出版信息

Medchemcomm. 2019 Jan 11;10(4):573-583. doi: 10.1039/c8md00484f. eCollection 2019 Apr 1.

DOI:10.1039/c8md00484f
PMID:31057737
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6482410/
Abstract

A series of tryptamine salicylic acid derivatives were synthesized and their antiproliferative activity against MGC-803, MCF-7, HepG2, A549 and HeLa cell lines was evaluated. The structure-activity relationship (SAR) study revealed that different substitutions of the C5 and C3'-C5' positions have certain effects on the anti-proliferation activity. The growth assay revealed that () showed the most potent and broad-spectrum anticancer inhibition of all the cell lines evaluated, and was only more potent than 5-Fu for the gastric cancer cell line. Preliminary studies indicated that compound could inhibit colony formation and migration of MGC-803 cells. The flow cytometry (FCM) results showed that compound arrested the cell cycle in the G2/M phase and induced apoptosis of MGC-803 cells in a concentration-dependent manner. In addition, the western blot results showed that can down-regulate the expression of hexokinase 2. Our studies suggest that the framework of may be consider as a new type of chemical for designing effective anti-cancer drugs targeting gastric cancer cells.

摘要

合成了一系列色胺水杨酸衍生物，并评估了它们对MGC-803、MCF-7、HepG2、A549和HeLa细胞系的抗增殖活性。构效关系（SAR）研究表明，C5和C3'-C5'位置的不同取代对抗增殖活性有一定影响。生长试验表明，（）对所有评估的细胞系均表现出最有效和广谱的抗癌抑制作用，且仅对胃癌细胞系的活性比5-氟尿嘧啶更强。初步研究表明，化合物可抑制MGC-803细胞的集落形成和迁移。流式细胞术（FCM）结果显示，化合物使细胞周期停滞在G2/M期，并以浓度依赖的方式诱导MGC-803细胞凋亡。此外，蛋白质印迹结果表明，可下调己糖激酶2的表达。我们的研究表明，（）的骨架可被视为一种新型化学物质，用于设计针对胃癌细胞的有效抗癌药物。