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.
Daoubi
Mourad
M
Departamento de Química Orgánica, Facultad de Ciencias, Universidad de Cádiz, Apdo. 40, 11510 Puerto Real, Cádiz, Spain.
Marquez
Nieves
N
Mazoir
Noureddine
N
Benharref
Ahmed
A
Hernández-Galán
Rosario
R
Muñoz
Eduardo
E
Collado
Isidro G
IG
D002453:Cell Cycle / Q000187:drug effects; D018360:Crystallography, X-Ray; D004224:Diterpenes / Q000302:isolation & purification* / Q000494:pharmacology*; D028481:Euphorbia / Q000737:chemistry*; D005434:Flow Cytometry; D015967:Gene Expression Regulation, Viral / Q000187:drug effects; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D007202:Indicators and Reagents; D019169:Jurkat Cells; D007840:Latex / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D010648:Phenylacetates / Q000302:isolation & purification* / Q000494:pharmacology*; D017550:Spectroscopy, Fourier Transform Infrared; D013141:Spiro Compounds / Q000302:isolation & purification* / Q000494:pharmacology*; D014315:Triterpenes / Q000302:isolation & purification* / Q000494:pharmacology*; D017735:Virus Latency / Q000187:drug effects*
D004224:Diterpenes; D007202:Indicators and Reagents; D007840:Latex; D010648:Phenylacetates; D013141:Spiro Compounds; D014315:Triterpenes