Three novel gnidimacrin related macrocyclic daphnanes (GMDs), daphneodorins A-C (2-4), were isolated from Daphne odora Thunb., together with gnidimacrin (1). Their structures were established by extensive physicochemical and spectroscopic analyses. Compounds 2 and 3 potently inhibited HIV-1 replication at subnanomolar concentrations (EC 50 0.16 and 0.25 nM, respectively). Compounds 2-4 represent a novel type of GMDs that are highly oxygenated on the macrocyclic ring, suggesting good potential for anti-HIV drug development by further chemical modification.
Structurally diverse tigliane diterpenoids
have drawn significant
research interest for drug discovery over many decades. Using LC-MS-guided
fractionation and separation, the first phytochemical investigation
on Wikstroemia lamatsoensis led to the isolation
of eight tiglianes (1–8), including
two new compounds, wikstrocin D (1) and wikstrocin E
(2). The new structures were elucidated based on extensive
physicochemical and spectroscopic analyses. The characteristic ESIMS/MS
fragmentations of tiglianes 1–8 were
also summarized. Among the isolated tiglianes, three compounds (8, 5, and 7) showed the most potent
anti-HIV activity, with IC50 values of 0.18, 3.8, and 12.8
nM, respectively.
Five new [daphneodorins D–H
(1, 5, and 10–12)] and seven known daphnane
diterpenoids (2–4 and 6–9) were isolated from Daphne odora. The structures of the new compounds were elucidated by extensive
physicochemical and spectroscopic analysis. The isolated compounds
were evaluated for their anti-HIV activity against HIV-1 infection
of MT4 cells. Nine daphnane diterpenoid orthoesters (1–9) showed potent anti-HIV activity with EC50 values of 1.5–7.7 nM.
From the whole plant of Daphne pedunculata, 12 macrocyclic daphnane diterpenoids, including six new compounds, daphnepedunins A−F (1−4, 9, and 10), were isolated. Their structures were elucidated by physiochemical and spectroscopic data analysis, the modified Mosher's method, and X-ray crystallography. The isolated compounds were evaluated for anti-HIV activity against HIV-1 infection in MT4 cells and showed significant anti-HIV activity with IC 50 values of 36.3−994 nM. A consideration of the anti-HIV activity of these compounds provided further insight into the structure−activity relationships of macrocyclic daphnane diterpenoids.
Macrocyclic daphnane orthoesters (MDOs) have attracted significant research interest for the drug discovery to cure HIV infection based on the "Shock and Kill" strategy. In the present study, the first chemical study on Wikstroemia ligustrina (Thymelaeaceae) was carried out by LC-MS analysis and phytochemical investigation. Nine daphnane diterpenoids (1−9) including seven MDOs were detected by LC-MS analysis. Further phytochemical investigation resulted in the isolation and structural elucidation of five daphnanes (1, 2, 5, 8, and 9) with potent anti-HIV activity. Taking the isolated MDO (1) as a model compound, the MS/MS fragmentation pathway was also elucidated.
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