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

Abstract

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 α-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 μM, meanwhile, compounds 1–18 displayed significant α-glucosidase inhibitory activities with IC50 values ranging from 3.28 ± 0.16 to 192.23 ± 0.78 μM. These research results imply that the separation and identification of these carbazole alkaloids showing notable PTP1B and α-glucosidase inhibitory activities from the fruits of C. anisum-olens can be very significant for discovering and developing new PTP1B inhibitors and α-glucosidase inhibitors for the treatment of diabetes mellitus.