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Uncarialins A–I, Monoterpenoid Indole Alkaloids from Uncaria rhynchophylla as Natural Agonists of the 5-HT₁A Receptor

Author:
Liang, Jia-Hao, Luan, Zhi-Lin, Tian, Xiang-Ge, Zhao, Wen-Yu, Wang, Ya-Li, Sun, Cheng-Peng, Huo, Xiao-Kui, Deng, Sa, Zhang, Bao-Jing, Zhang, Zhan-Jun, Ma, Xiao-Chi
Source:
Journal of natural products 2019 v.82 no.12 pp. 3302-3310
ISSN:
1520-6025
Subject:
Uncaria rhynchophylla, agonists, amino acids, circular dichroism spectroscopy, computer simulation, indole alkaloids, mechanism of action, median effective concentration, monoterpenoids, nuclear magnetic resonance spectroscopy
Abstract:
Nine new monoterpenoid indole alkaloids, uncarialins A–I (1–9), were isolated from Uncaria rhynchophylla as 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 22 displayed significant agonistic effects against the 5-HT₁A receptor with EC₅₀ 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-HT₁A 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.
Agid:
6794527