Improved synthesis and in vitro evaluation of the cytotoxic profile of oxysterols oxidized at C4 (4α- and 4β-hydroxycholesterol) and C7 (7-ketocholesterol, 7α- and 7β-hydroxycholesterol) on cells of the central nervous system

摘要: Abstract Whereas the biological activities of oxysterols oxidized at C7 (7-ketocholesterol (7KC), 7β-hydroxycholesterol (7β-OHC), 7α-hydroxycholesterol (7α-OHC)) are well documented, those C4 (4β-hydroxycholesterol (4β-OHC), 4α-hydroxycholesterol (4α-OHC)) not known, especially on cells central nervous system. Therefore, an improved methodology has been validated for 4β-OHC and 4α-OHC synthesis, effects cell viability growth these molecules were studied immortalized, tumoral normal brain (158N, C6 SK-N-BE cells, mixed primary cultures astrocytes oligodendrocytes). inhibition with 7KC, 7β-OHC, 7α-OHC is associated a decrease (cytotoxic activities), our data establish that have no effect viability, or minor evocating cytostatic properties. Thus, comparatively to C7, toxicity in following range order: 7KC ≥ 7β-OHC > 7α-OHC > (4β-OHC ≥ 4α-OHC). Interestingly, date, only identified properties suggesting molecules, whereas cytotoxic, may some interests counteract proliferation.