2-Acylpyrrole-based alkaloids from the leaves of Sauropus spatulifolius and their α-glucosidase inhibitory activities

Pyrrole alkaloids are a class of natural products with intriguing structures and promising biological actives. Within the Sauropus plants, these alkaloids are mainly present in Sauropus spatulifolius. An investigation of the leaves of S. spatulifolius was conducted to discover novel and bioactive pyrrole alkaloids. This study led to the identification of 38 alkaloids, including 21 new pyrrole alkaloids (1 − 5, 13, 16, 19 − 23, 26 − 31, 33, 35, and 36), along with 17 related analogues (6 − 12, 14, 15, 17, 18, 24, 25, 32, 34 37, and 38). The structures of the new compounds were elucidated by NMR, HRESIMS, electronic circular dichroism (ECD), and X-ray diffraction analysis. Notably, compounds 28 − 31 were identified as pyrrole alkaloids with unprecedented skeletons. Compounds 28 and 29 featured a 2-acylpyrrole alkaloid and a cinnamic acid heterodimers, while 30 and 31 possessed a pyrrolooxazinone scaffold with a 1,2-hexadecanediol moiety. These structures were rare in plants. Three compounds (27, 31, and 38) displayed α-glucosidase inhibitory activity. Particularly, compounds 27 (IC₅₀: 320.3 μM) and 31 (IC₅₀: 153.7 μM) exhibited stronger activity than that of acarbose (IC₅₀: 545.9 μM). Molecular docking studies showed the strong interactions of the three bioactive compounds with the α-glucosidase protein. Additionally, compounds 27, 31, and 38 showed significant effects on enhancing glucose consumption in HepG2 cells.