Isolation of new phenylacetylingol derivatives that reactivate HIV-1 latency and a novel spirotriterpenoid from Euphorbia officinarum latex

Three new, highly functionalized ingol diterpenes, ingol 7,8,12-triacetate 3-phenylacetate (1), ingol 7,8,12-triacetate 3-(4-methoxyphenyl)acetate (2) and 8-methoxyingol 7,12-diacetate 3-phenylacetate (3), together with the novel spirotriterpene, 3S,4S,5R,7S,9R,14R-3,7-dihydroxy-4,14-dimethyl-7[8 → 9]-Abeo-cholestan-8-one (4), have been isolated from Euphorbia officinarum latex. Structures were established on the basis of their spectroscopic data, including two-dimensional NMR analysis and NOE experiments. The biological effects of 1–3 on cell cycle and HIV-1 gene transcription were analysed in the Jurkat T cell line. Compound 3 induced cell-cycle arrest and HIV-1-LTR promoter activation and could represent a novel lead compound for the development of therapies against HIV-1 latency.

Graphical abstractThe biological effects of new ingol diterpenes (1–3) on cell cycle and HIV-1 gene transcription were analysed. Compound 3 induced cell-cycle arrest and HIV-1-LTR promoter activation.Figure optionsDownload full-size imageDownload as PowerPoint slide