posted on 2021-04-29, 08:41authored byJoão
B. F. Tostes, Andressa L. D. Carvalho, Antonio J. Ribeiro da Silva, Pedro Junior P. Mourão, Átila D. Rossi, Amílcar Tanuri, Antonio C. Siani
Three
known compounds, 20-deoxyphorbol-5β-hydroxy-12-tiglate-13-isobutyrate
(1), 20-deoxyphorbol-5β-hydroxy-12-tiglate-13-phenylacetate
(2), and 4-deoxy-4β-phorbol-12-tiglate-13-phenylacetate
(3), were reisolated from the latex of Euphorbia
umbellata through a bioguided fractionation process to target
HIV-1 latency reactivation. The in vitro bioassay using infected T-cell
lymphoblasts (J-Lat 10.6), complemented with surface CD4 receptor
downregulation assessment, led to isolation of the compounds as a
highly active ternary mixture. Effective purification of the individual
compounds was achieved by first subjecting a phorbol-enriched fraction
(previously prepared from crude latex) to MPLC, followed by semipreparative
HPLC and characterization by 1D and 2D NMR spectroscopy and (+)-HRESIMS.
Compared with a positive control, the isolated compounds were effective
in reactivating 68–75% of the virus latency in the range of
9.7–0.097 μM for compound 1, 8.85–0.088 μM for compound 2, and 9.1–0.091 μM for compound 3, with the latter maintaining steady effectiveness down to
a 10–5 dilution. Accordingly, compound 3 may serve as a promising lead compound for the development of anti-HIV
drugs based on latency reactivation therapy.