Synthesis and biological evaluation of novel derivatives of gambogenic acid as anticancer agents

Abstract

A series of novel derivatives of gambogenic acid (GNA) were synthesized and evaluated for their in vitro antiproliferative activity against four kinds of tumor cell lines. The compounds 3c, 3f, 3h and 3j displayed potent antiproliferative activities (IC₅₀: 1.41–2.94 μM on A549 cells, 0.98–1.95 μM on HepG2 cells, 0.45–2.86 μM on panc-1 cells and 1.13–2.65 μM on U251 cells), which are superior to those of the parent compound GNA. Note that 3f significantly affects the proliferation of tumor cells. Furthermore, 3f could induce S phase cell cycle arrest and decrease the ratio of Bc1-2/Bax in HepG2 cells. This suggests that 3f may serve as a potential lead compound for the development of new anticancer drugs.