Skip to Main content Skip to Navigation
Journal articles

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

Abstract : Whereas the biological activities of oxysterols oxidized at C7 (7-ketocholesterol (71(C), 76-hydroxycholesterol (7 6-0HC), 7 alpha-hydroxycholesterol (7 alpha-OHC)) are well documented, those of oxysterols oxidized at C4 (4 beta-hydroxycholesterol (4 beta-OHC), 4 alpha-hydroxycholesterol (4 alpha-OHC)) are not well known, especially on the cells of the central nervous system. Therefore, an improved methodology has been validated for 4 beta-OHC and 4 alpha-OHC synthesis, and the effects on cell viability and cell growth of these molecules were studied on immortalized, tumoral and normal brain cells (158N, C6 and SK-N-BE cells, and mixed primary cultures of astrocytes and oligodendrocytes). Whereas inhibition of cell growth with 7KC, 7 6-OHC, and 7 alpha-OHC is associated with a decrease of cell viability (cytotoxic activities), our data establish that 4 beta-OHC and 4a-OHC have no effect on cell viability, and no or minor effect on cell growth evocating cytostatic properties. Thus, comparatively to oxysterols oxidized at C7, the toxicity of oxysterols oxidized at C4 is in the following range of order: 7KC > 76-OHC > 7 alpha-OHC > (4 alpha-OHC > 4 alpha-OHC). Interestingly, to date, 4 beta-0HC and 4a-OHC are the only oxysterols identified with cytostatic properties suggesting that these molecules, whereas not cytotoxic, may have some interests to counteract cell proliferation.
Complete list of metadata

https://hal.univ-lorraine.fr/hal-01518904
Contributor : Lcp-A2mc Ul Connect in order to contact the contributor
Submitted on : Friday, May 5, 2017 - 3:29:29 PM
Last modification on : Tuesday, July 24, 2018 - 11:45:21 AM

Identifiers

Citation

Thomas Nury, Mohammad Samadi, Amira Zarrouk, Jean Marc Riedinger, Gérard Lizard. Improved synthesis and in vitro evaluation of the cytotoxic profile of oxysterols oxidized at C4 (4 alpha- and 4 beta-hydroxycholesterol) and C7 (7-ketocholesterol, 7 alpha- and 7 beta-hydroxycholesterol) on cells of the central nervous system. European Journal of Medicinal Chemistry, Elsevier, 2013, 70, pp.558-567. ⟨10.1016/j.ejmech.2013.09.028⟩. ⟨hal-01518904⟩

Share

Metrics

Record views

227