Abstract
Protein farnesyltransferase (FTase) has recently appeared as a new target of parasitic diseases, a field poor in drugs in development. With the aim of creating new bisubstrate inhibitors of FTase, new farnesyl pyrophosphate analogues have been studied. Farnesyl analogues with a malonic acid function exhibited the best inhibitory activity on FTase. This group was introduced into our imidazole-containing model leading to new compounds with submicromolar activities. Kinetic experiments have been realized to determine their binding mode to the enzyme.
Copyright 2009 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Binding Sites
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Cell Line, Tumor
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Cell Proliferation / drug effects
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Drug Screening Assays, Antitumor
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Farnesyltranstransferase / antagonists & inhibitors*
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Humans
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Kinetics
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Molecular Structure
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Parasitic Sensitivity Tests
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Plasmodium falciparum / drug effects
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Plasmodium falciparum / growth & development
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Polyisoprenyl Phosphates / chemical synthesis*
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Polyisoprenyl Phosphates / chemistry
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Polyisoprenyl Phosphates / pharmacology*
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Sesquiterpenes / chemical synthesis*
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Sesquiterpenes / chemistry
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Sesquiterpenes / pharmacology*
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Stereoisomerism
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Structure-Activity Relationship
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Trypanosoma brucei brucei / drug effects
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Trypanosoma brucei brucei / growth & development
Substances
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Polyisoprenyl Phosphates
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Sesquiterpenes
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farnesyl pyrophosphate
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Farnesyltranstransferase