Identification of anti-HIV cycloartane triterpenoids from Actaea vaginata using UPLC‐QTOF‐MS/MS, DFT calculations, docking, and molecular dynamics studies

Structurally diverse triterpenoids have shown potential as pharmaceutical precursors for HIV treatment. Our previous research led to the discovery of a potent antiviral cycloartane triterpenoid derivative, (20S,24S)-15β,16β-diacetoxy-18,24;20,24-diepoxy-9,19-cyclolanostane-3β,25-diol 3-O-3′,3′-dimethyl succinate (DSC) derived from the triterpene glycoside beesioside I, exhibiting high-affinity interactions with the Capsid (CA) and spacer peptide 1 (SP1) domain (CA-SP1) region of the HIV Gag polyprotein. To discover new antiviral agents from natural resources, the methanolic extracts of Actaea vaginata were qualitatively analyzed using UPLC-QTOF-MS/MS. Based on characteristic ESIMS/MS fragmentations of cycloartane triterpenoids obtained from A. vaginata and relevant literature, twenty-one compounds including an unknown triterpenoid (1) were identified. Guided by LC-MS analysis, compound 1 was isolated and determined as (20S,24S)-15β,16β-diacetoxy-18,24;20,24-diepoxy-9,19-cyclanostane-3β,25-diol-3-O-β-d-xylopyranosyl-25-O-β-d-glucopyranoside by spectroscopic methods, showing moderate antiviral activity with an EC₅₀ value of 8.6 µM against HIV-1_NL-43 in MT4 cells. The structural data and electronic properties of compound 1 were determined using the B3LYP density functional method with the basis set 6–311+G(d,p). To further understand the compound's antiviral quality, molecular docking and molecular dynamics studies were conducted. The results indicated that compound 1 could be a potential candidate for anti-HIV treatment.