Acylation of 25-hydroxyprotopanaxatriol with aromatic acids increases cytotoxicity.

20(R)-25-hydroxyprotopanaxadiol (25-OH-PPD) is a natural compound showing a variety of anti-tumor effects. In an attempt to search for a new anti-cancer compound with higher antitumor activities, we designed and synthesized a series of 25-OH-PPD derivatives. Cytotoxicity assay of these derivatives towards MCF-7, A549, U87, HO-8901, Hela cancer cell lines and normal IOSE144 cell lines were tested by MTT assay. Results showed that compared with compound 25-OH-PPD, Compounds 4, 5, 6, 10, 11 showed strong anticancer activity, and all compounds showed low toxicity or no toxicity for normal cells. In particular, compound 6 exhibited the best anti-tumor activity in all cancer cell lines (MCF-7, A549, U87, HO-8901, and Hela) with IC values of 5.04 μM, 1.36 μM, 3.24 μM, 3.47 μM, 4.57 μM, respectively. Among the five cell lines, all the compounds showed strong inhibition on A549 cells. Further studies showed that Compound 6 significantly inhibited the proliferation of A549 cells by inducing apoptosis. Our results indicate that Compound 6 is a potential anticancer inhibitor and provides a theoretical basis for further research.