Structurally diverse dammarane-derived triterpenoids from the twigs of Aglaia perviridis Hiern and their α-glucosidase and PTP1B inhibitory activities

This study aimed to investigate the chemical constituents of the twigs of Aglaia perviridis and their potential health benefits. A total of 29 triterpenoids, including eight previously undescribed dammarane triterpenoids, perviridisins A (1) and D-J (4-10), two unusual abeo-dammarane triterpenoids, perviridisins B (2) and C (3), and five unidentified nordammarane triterpenoids, perviridisins K-O (11-15), along with 14 known analogues (16-29), were isolated from the twigs of A. perviridis. Their structures with absolute configurations were elucidated based on a combination of extensive spectroscopic data analyses, chemical methods, electronic circular dichroism (ECD), Mo2(OAc)4-induced electronic circular dichroism (IECD), and calculated NMR with DP4+ probability analysis, as well as comparison with previously reported NMR data. Notably, perviridisin A (1) possesses a novel 6/6/6/5/7/5 hexacyclic ring system decorated with an unprecedented bridged 2,3,9-trioxabicyclo[4.2.1]nonane scaffold bearing a peroxide bridge, and perviridisins B (2) and C (3) represent the fourth reported examples of naturally occurring 23(24 -> 25)abeo-dammaranes. Perviridisin O (15) was characterized by the unique position of a hydroxy group at C-13, which had never been discovered in natural dammarane-type triterpenoids before. All the isolates were evaluated for their in vitro inhibitory effects on alpha-glucosidase and protein tyrosine phosphatase 1 B (PTP1B) as well as cytotoxicities against four human carcinoma cell lines (A549, HT-29, SNU-398, and Capan-1). Compounds 6, 8-12, 16, 26, and 29 showed inhibitory activity against alpha-glucosidase with IC50 values of 68.2-295.2 mu M, 2-10 times stronger than that of the positive control acarbose (733.4 mu M); meanwhile, 1, 3, 7-10, 13, and 26-29 exhibited varying degrees of PTP1B inhibition with IC50 values ranging from 4.7 to 19.5 mu M. Additionally, compound 27 showed moderate cytotoxicity against the HT- 29 cells with an IC50 value of 8.4 mu M. These findings indicated that dammarane-type triterpenoids have potential as pharmaceutical drug leads for preventing and treating diabetes.