Abstract
A series of aminopropylindenes, designed as mimics of a cationic high energy intermediate in the oxidosqualene cyclase(1) (OSC)-mediated cyclization of 2,3-oxidosqualen to lanosterol was prepared from Grundmann's ketone. Screening on OSCs from five different organisms revealed interesting activities and selectivities of some of the compounds. A N,N-dimethylaminopropyl derivative showed promising inhibition of Trypanosoma cruzi OSC in combination with low cytotoxicity, and showed significant reduction of cholesterol biosynthesis in a human cell line.
Copyright © 2013. Published by Elsevier Masson SAS.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Arabidopsis / drug effects
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Arabidopsis / enzymology
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Biocatalysis / drug effects
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Cell Survival / drug effects
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Cholesterol / biosynthesis
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Dose-Response Relationship, Drug
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Enzyme Inhibitors / chemistry*
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Enzyme Inhibitors / metabolism
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Enzyme Inhibitors / pharmacology*
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HL-60 Cells
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Humans
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Inhibitory Concentration 50
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Intramolecular Transferases / antagonists & inhibitors*
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Intramolecular Transferases / metabolism
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Ketones / chemistry*
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Ketones / metabolism
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Lanosterol / chemistry
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Lanosterol / metabolism
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Models, Chemical
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Molecular Structure
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Plant Proteins / antagonists & inhibitors
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Plant Proteins / metabolism
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Protozoan Proteins / antagonists & inhibitors
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Protozoan Proteins / metabolism
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Squalene / chemistry
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Squalene / metabolism
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Trypanosoma cruzi / drug effects
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Trypanosoma cruzi / enzymology
Substances
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Enzyme Inhibitors
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Ketones
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Plant Proteins
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Protozoan Proteins
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Lanosterol
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Squalene
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Cholesterol
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Intramolecular Transferases
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lanosterol synthase