Carbazole alkaloids from the fruits of Clausena anisum-olens with potential PTP1B and α-glucosidase inhibitory activities

The phytochemical investigation on the fruits of Clausena anisum-olens led to the isolation of 18 carbazole alkaloids (1-18), containing three new ones, clausenanisines A-C (1-3), and three new naturally occurring carbazole alkaloids, clausenanisines D-F (4-6), as well as 12 known analogues (7-18). The chemical structures of clausenanisines A-F (1-6) were elucidated by extensive spectroscopic methods. Notably, clausenanisine A (1) was a novel carbazole alkaloid with a unique five-membered cyclic ether, while clausenanisine E (5) is an unusual carbazole alkaloid owning an unprecedented naturally occurring carbon skeleton possessing 14 carbon atoms. The known carbazole alkaloids (7-18) were identified by the comparison of their spectral data with those data reported in the literature. All known carbazole alkaloids 7-18 were isolated from C. anisum-olens for the first time. Moreover, all isolated compounds 1-18 were assessed for their protein tyrosine phosphatase 1B (PTP1B) and alpha-glucosidase inhibitory activities in vitro. Compounds 1-18 exhibited remarkable PTP1B inhibitory activities with IC50 values in the range of 0.58 +/- 0.05 to 38.48 +/- 0.32 mu M, meanwhile, compounds 1-18 displayed significant alpha-glucosidase inhibitory activities with IC5(0) values ranging from 3.28 +/- 0.16 to 192.23 +/- 0.78 mu M. These research results imply that the separation and identification of these carbazole alkaloids showing notable PTP1B and alpha-glucosidase inhibitory activities from the fruits of C. anisum-olens can be very significant for discovering and developing new PTP1B inhibitors and alpha-glucosidase inhibitors for the treatment of diabetes mellitus.