Uncarialins A–I, Monoterpenoid Indole Alkaloids from Uncaria rhynchophyllaas Natural Agonists of the 5-HT1AReceptor

Nine new monoterpenoid indole alkaloids, uncarialins A–I (1–9), were isolated from Uncaria rhynchophyllaas well as 14 known analogues (10–23). Their structures were determined by HRESIMS, 1D and 2D NMR, and experimental and calculated electronic circular dichroism data. Compounds 5, 7, 15, and 22displayed significant agonistic effects against the 5-HT1Areceptor with EC50values of 2.2 ± 0.1, 0.1 ± 0.1, 1.6 ± 0.3, and 2.0 ± 0.5 μM, respectively. The mechanisms of action of these four compounds with the 5-HT1Areceptor were investigated by molecular docking, and the results suggested that amino acid residues Asp116, Thr196, Asn386, and Tyr390 played critical roles in the observed activity of the above-mentioned compounds.