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

The 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. 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, 3 S,4 S,5 R,7 S,9 R,14 R-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.