Brucella suis histidinol dehydrogenase: Synthesis and inhibition studies of a series of substituted benzylic ketones derivated from histidine
| Autor: | Stephan Köhler, Rose-Anne Boigegrain, Pascale Joseph, Marie-Rose Abdo, Jean-Yves Winum, Jean-Louis Montero, Jean-Pierre Liautard |
|---|---|
| Přispěvatelé: | Institut des Biomolécules Max Mousseron [Pôle Chimie Balard] (IBMM), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM), Centre d’études d’Agents Pathogènes et Biotechologies pour la Santé (CPBS), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 2007 |
| Předmět: |
Brucella suis
Clinical Biochemistry Pharmaceutical Science Brucellaceae Brassica Brucella 01 natural sciences Biochemistry Histidinol dehydrogenase Microbiology 03 medical and health sciences Bacterial Proteins Benzyl Compounds Drug Discovery Escherichia coli Histidine Cloning Molecular Enzyme Inhibitors Molecular Biology Pathogen 030304 developmental biology Antibacterial agent 0303 health sciences biology 010405 organic chemistry Chemistry [CHIM.ORGA]Chemical Sciences/Organic chemistry Organic Chemistry Biological activity Ketones biology.organism_classification 0104 chemical sciences 3. Good health Alcohol Oxidoreductases Molecular Medicine Electrophoresis Polyacrylamide Gel Indicators and Reagents |
| Zdroj: | Bioorganic and Medicinal Chemistry Bioorganic and Medicinal Chemistry, Elsevier, 2007, 15, pp.4427-4433. ⟨10.1016/j.bmc.2007.04.027⟩ |
| ISSN: | 0968-0896 1464-3391 |
| DOI: | 10.1016/j.bmc.2007.04.027⟩ |
| Popis: | Brucella spp. is the causative agent of brucellosis (Malta fever), which is the most widespread zoonosis worldwide. The pathogen is capable of establishing persistent infections in humans which are extremely difficult to eradicate even with antibiotic therapy. Moreover, Brucella is considered as a potential bioterrorism agent. Histidinol dehydrogenase (HDH, EC 1.1.1.23) has been shown to be essential for the intramacrophagic replication of this pathogen. It therefore constitutes an original and novel target for the development of anti-Brucella agents. In this work, we cloned and overexpressed the HDH-encoding gene from Brucella suis, purified the protein and evidenced its biological activity. We then investigated the inhibitory effects of a series of substituted benzylic ketones derived from histidine. Most of the compounds reported here inhibited B. suis HDH in the lower nanomolar range and constitute attractive candidates for the development of novel anti-Brucella agents. |
| Databáze: | OpenAIRE |
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