Synthesis and antitumor activity evaluation of glycoconjugates derived from natural product harmine
10.11665/j.issn.1000-5048.2023041101
- VernacularTitle:天然产物去氢骆驼蓬碱糖基偶联物的合成及抗肿瘤活性评价
- Author:
Xiaohan LIU
1
;
Yunying TAN
;
Qiang LI
;
Xu CHEN
;
Junjie FU
;
Jian YIN
Author Information
1. 江南大学生物工程学院糖化学与生物技术教育部重点实验室
- Publication Type:Journal Article
- Keywords:
harmine;
2-amino-2-deoxy-D-glucose;
glycoconjugate drugs;
antitumor activity
- From:
Journal of China Pharmaceutical University
2023;54(6):729-742
- CountryChina
- Language:Chinese
-
Abstract:
Based on our previous work, the study herein designed and synthesized eight glycoconjugates of natural product harmine (14a-14h)by introducing a cyclohexylmethyloxyl group at its C7 position and coupling a methyl-2-amino-β-D-glucopyranoside to the N9 position through different lengths of alkyl chains.In vitro anti-tumor activity screening and structure-activity relationship studies showed that the antitumor activity of the conjugates increased with the lengthening of the alkyl chain in the linker.Compound 14h exhibited significantly better proliferative inhibitory activity against MDA-MB-231 breast cancer cells than harmine.As compared to harmine, the introduction of the carbohydrate moiety improved the water solubility of compound 14h and enhanced its tumor cell selectivity through the Warburg effect.Mechanism of action studies revealed that compound 14h induced apoptosis and G0/G1 cell cycle arrest in MDA-MB-231 cells, and inhibited tumor cell migration by interfering with epithelial-mesenchymal transition process.This study provides a new approach for the development of antitumor drugs based on harmine.
