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
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.