Pharmacologic studies have revealed that polycyclic polyprenylated acylphloroglucinols (PPAPs) collectively exhibit a broad range of biological activities, including antineoplastic potential. Here, six new PPAPs, named garcixanthochymones F-K (3, 5, 7, 8, 11, and 15), together with nine known analogues were isolated from the fruits of Garcinia xanthochymus. Their structures were elucidated based on the spectroscopic data, including UV, HRESIMS, and NMR, and quantum chemical calculations. All the isolated PPAPs were tested for anti-proliferative activity against four human tumor cell lines, including SGC7901, A549, HepG2, and MCF-7. Most of the PPAPs possessed high anti-proliferative activity with IC50 values in the range of 0.89 to 36.98 μM, and significant apoptosis was observed in MCF-7 cells exposed to compounds 2 and 5. Besides, docking results showed that compounds 2 and 5 could strongly combine with the Src homology 2 (SH2) domain of STAT3 via hydrogen bond and hydrophobic interaction, which is one of the key oncogenes and crucial therapeutic targets. Furthermore, compounds 2 and 5 efficiently downregulated the expression of p-STAT3Tyr705 and pivotal effector proteins involved in oncogenic signaling pathways of MCF-7 cells.
Keywords: Garcinia xanthochymus; STAT3; anti-proliferative; apoptosis; polycyclic polyprenylated acylphloroglucinols.