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Design and Synthesis of Novel Anti-Proliferative Emodin Derivatives and Studies on their Cell Cycle Arrest, Apoptosis Pathway and Migration

Authors :
Kun Yang
Ming-Ji Jin
Zhe-Shan Quan
Hu-Ri Piao
Source :
Molecules, Vol 24, Iss 5, p 884 (2019)
Publication Year :
2019
Publisher :
MDPI AG, 2019.

Abstract

Emodin is a cell arrest and apoptosis-inducing compound that is widely distributed in different plants (rhubarb, aloe), lichens and terrestrial fungi, and also isolated from marine-derived fungi and marine sponge-associated fungi. In this study, we designed and synthesized a novel series of emodin derivatives by binding emodin to an amino acid using linkers of varying lengths and composition, and evaluated their anti-proliferative activities using HepG2 cells (human hepatic carcinoma), MCF-7 cells (human breast cancer) and human normal liver L02 cells. Most of these derivatives showed moderate to potent anti-proliferative activities. Notably, compound 7a exhibited potent anti-proliferative activity against HepG2 cells with the half maximal inhibitory concentration (IC50) value of 4.95 µM, which was enhanced 8.8-fold compared to the parent compound emodin (IC50 = 43.87 µM), and it also exhibited better selective anti-proliferative activity and specificity than emodin. Moreover, further experiments demonstrated that compound 7a displayed a significant efficacy of inducing apoptosis through mitochondrial pathway via release of cytochrome c from mitochondria and subsequent activation of caspase-9 and caspase-3, inducing cell arrest at G0/G1 phase, as well as suppression of cell migration of tumor cells. The preliminary results suggested that compound 7a could be a promising lead compound for the discovery of novel anti-tumor drugs and has the potential for further investigations as an anti-cancer drug.

Details

Language :
English
ISSN :
14203049
Volume :
24
Issue :
5
Database :
Directory of Open Access Journals
Journal :
Molecules
Publication Type :
Academic Journal
Accession number :
edsdoj.149527bdd2864d6191ca8b0f2c630322
Document Type :
article
Full Text :
https://doi.org/10.3390/molecules24050884