Search

Piperazinone nucleosides can be formed by N-glycosylation with 1-O-acetyl-2,3,5-tri-O-benzoyl-β-D-ribofuranose of either piperazin-2-ones or pyrazin-2-ones followed by reduction of the heterocycle with rhodium on alumina. All the prepared compounds were tested for their activity against the Visna virus, but did not show significant antiviral activity.

Various 5-alkyl-6-aza-5,6-dihydrouridines and 6-(β-D-ribopyranosyl)-5-alkyl-6-aza-5,6-dihydrouracils have been synthesized. A new regioselective method is described for coupling triazinic bases to the sugar unit. Different epimers were isolated. Antiretroviral activity against Visna virus was evaluated.

Glycosylation of 3-alkyl N 4 -(3-hydroxypropyl) 2-piperazinones by protected 1- O -acetyl ribofuranoses produces nucleoside analogs in which the base is separated from the sugar by a hydrocarbon spacer arm. The preliminary in vitro test results against retroviruses seem promising for compounds bearing a long alkyl chain.

Various 5-alkyl-6-aza-5,6-dihydrouridine were synthesized from the corresponding triazinic heterocycles and acetylated ribose. These nucleosides were tested for inhibitory activity on lentivirus Visna-Maedi.

International audience; Non-steroidal anti-inflammatory drugs (NSAIDs) have been shown to produce an anti-proliferative and pro-apoptotic effect on different types of cancer cell lines. Previously, we demonstrated that high dose of NS-398 (100 microM), a selective cyclooxygenase-2 inhibitor, induced a cell cycle slowing or arrest and, in contrast to low dose (10 microM), a marked decrease in apoptosis in human 1547 osteosarcoma cells. In this study, we investigated particularly the effect of 100 microM NS-398 on p53 and p21 expression, caspase activities and nuclear factor-kappaB (NF-kappaB). We found a correlation between p53, p21 mRNA expression and NF-kappaB activation and, we observed an induction of heat shock protein 70 expression with a large decrease in caspase-3 activity after 100 microM NS-398 treatment. Moreover, the inhibition of apoptosis was correlated with an increase in bcl-2/bax ratio. Our new findings confirm the novel anti-apoptotic property of NS-398 at 100 microM, as we previously found, which contrasts to the described NS-398 pro-apoptotic effect on other cancer cell lines.