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.
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Authors | Stéphanie Duez, Laëtitia Coudray, Elisabeth Mouray, Philippe Grellier, Joëlle Dubois |
Journal | Bioorganic & medicinal chemistry
(Bioorg Med Chem)
Vol. 18
Issue 2
Pg. 543-56
(Jan 15 2010)
ISSN: 1464-3391 [Electronic] England |
PMID | 20036564
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright 2009 Elsevier Ltd. All rights reserved. |
Chemical References |
- Polyisoprenyl Phosphates
- Sesquiterpenes
- farnesyl pyrophosphate
- Farnesyltranstransferase
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Topics |
- Binding Sites
- Cell Line, Tumor
- Cell Proliferation
(drug effects)
- Drug Screening Assays, Antitumor
- Farnesyltranstransferase
(antagonists & inhibitors)
- Humans
- Kinetics
- Molecular Structure
- Parasitic Sensitivity Tests
- Plasmodium falciparum
(drug effects, growth & development)
- Polyisoprenyl Phosphates
(chemical synthesis, chemistry, pharmacology)
- Sesquiterpenes
(chemical synthesis, chemistry, pharmacology)
- Stereoisomerism
- Structure-Activity Relationship
- Trypanosoma brucei brucei
(drug effects, growth & development)
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