Abstract
4 alpha-(2-Propenyl)-5 alpha-cholestan-3 alpha-ol (LY295427) was previously identified from a CHO cell-based assay to be a potent LDL receptor up-regulator and had demonstrated to be an effective agent in lowering plasma cholesterol levels in hypercholesterolemic hamsters. In order to investigate the effect of flexibility of the 3 alpha-hydroxy-bearing A-ring on the activity, 4 alpha-(2-propenyl)-5,6-secocholestan-3 alpha-ol (11), a B-ring seco analog of LY295427, is thus synthesized from cholest-4-en-3-one. Test results indicate that 11 is not active in the CHO cell-based LDL receptor/luciferase assay at concentrations up to 20 micrograms/mL. The result underlines the importance of maintaining the A-B-C-D ring rigidity of the 3 alpha-sterols in terms of binding to the putative oxysterol receptor.
MeSH terms
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Animals
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Anticholesteremic Agents / chemical synthesis
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Anticholesteremic Agents / chemistry*
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Anticholesteremic Agents / pharmacology
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CHO Cells
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Cholestanol / analogs & derivatives*
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Cholestanol / chemical synthesis
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Cholestanols / chemical synthesis
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Cholestanols / chemistry*
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Cholestanols / pharmacology
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Cholestenones / metabolism
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Cricetinae
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Gene Expression Regulation / drug effects
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Genes, Reporter
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Hydroxycholesterols / pharmacology
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Luciferases / genetics
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Luciferases / metabolism
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Promoter Regions, Genetic
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Receptors, LDL / biosynthesis
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Receptors, LDL / genetics
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Structure-Activity Relationship
Substances
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2-propenyl-5,6-secocholestan-3-ol
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Anticholesteremic Agents
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Cholestanols
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Cholestenones
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Hydroxycholesterols
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LY 295427
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Receptors, LDL
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cholest-4-en-3-one
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25-hydroxycholesterol
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Cholestanol
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Luciferases