Uncarialins A-I, Monoterpenoid Indole Alkaloids from as Natural Agonists of the 5-HT Receptor.

Nine new monoterpenoid indole alkaloids, uncarialins A-I (-), were isolated from as well as 14 known analogues (-). Their structures were determined by HRESIMS, 1D and 2D NMR, and experimental and calculated electronic circular dichroism data. Compounds , , , and displayed significant agonistic effects against the 5-HT receptor with EC values 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-HT receptor 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.