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Anti-Cancer Agents in Medicinal Chemistry


ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

Research Article

Discovery of a Highly Potent and Novel Gambogic Acid Derivative as an Anticancer Drug Candidate

Author(s): Huiping Ling, Hong Li, Meijun Chen, Baolong Lai, Haiming Zhou, Hui Gao, Jiangye Zhang, Yan Huang* and Yiwen Tao*

Volume 21, Issue 9, 2021

Published on: 08 April, 2020

Page: [1110 - 1119] Pages: 10

DOI: 10.2174/1871520620666200408080040

Price: $65


Background and Purpose: Gambogic Acid (GA), a promising anti-cancer agent isolated from the resin of Garcinia species in Southeast Asia, exhibits high potency in inhibiting a wide variety of cancer cells’ growth. Moreover, the fact that it is amenable to chemical modification makes GA an attractive molecule for the development of anti-cancer agents.

Methods: Gambogic acid-3-(4-pyrimidinyloxy) propyl ester (compound 4) was derived from the reaction between 4-hydroxypropoxy pyrimidine and GA. Its structure was elucidated by comprehensive analysis of ESIMS, HRESIMS, 1 D NMR data. Anti-tumor activities of compound 4 and GA in vitro against HepG-2, A549 and MCF-7 cells were investigated by MTT assay. FITC/PI dye was used to test apoptosis. The binding affinity difference of compound 4 and GA binding to IKKβ was studied by using Discovery Studio 2016.

Results: Compound 4 was successfully synthesized and showed strong inhibitory effects on HepG-2, A549 and MCF-7 cells lines with an IC50 value of 1.49±0.11, 1.37±0.06 and 0.64±0.16μM, respectively. Molecular docking study demonstrated that four more hydrogen bonds were established between IKKβ and compound 4, compared with GA.

Conclusion: Our results suggested that compound 4 showed significant effects in inducing apoptosis. Further molecular docking study indicated that the introduction of pyrimidine could improve GA’s binding affinity to IKKβ. Compound 4 may serve as a potential lead compound for the development of new anti-cancer drugs.

Keywords: Gambogic acid derivatives, molecular docking, anti-tumor activity, HepG-2 cells, A549 cells, MCF-7 cells.

Graphical Abstract
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