Isolation, structure determination and structure–activity relationship of anti-toxoplasma triterpenoids from Quercus crispula Blume outer bark

Abstract

Toxoplasma gondii is an intracellular protozoan parasite of which infection can result in serious symptoms for fetuses or people who have weakened immune system. In our effort to discover novel anti-toxoplasma substances from tree barks, only outer bark extract from Quercus crispula Blume (mizunara) was revealed to show potent anti-toxoplasma activity. Isolation of the active principles was performed to identify three pentacyclic triterpenoids, namely 29-norlupane-3,20-dione, oleanolic acid acetate and ursolic acid acetate. These structures were determined by combining a series of spectral data, computational simulation and synthetic approach. All isolated compounds exhibited notable activities at IC50 of 6.8–24.4 μM and high selectivities against the parasite. The structure–activity relationship study conducted to probe key structure(s) indicated that the lack of free hydroxyl group at 3-position highly contributes to both the titer of activity and the selectivity. Moreover, skeleton and functionalities of E-rings were also suggested to affect to the activity. The present study demonstrated not only that the extract from Q. crispula Blume could be a promising source of toxoplasmacidal agent, but also that related extractive triterpenoids can be modified to furnish anti-toxoplasma activity.