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Article Dans Une Revue Journal of Medicinal Chemistry Année : 2007

Discovery and Refinement of a New Structural Class of Potent Peptide Deformylase Inhibitors.

Résumé

New classes of antibiotics are urgently needed to counter increasing levels of pathogen resistance. Peptide deformylase (PDF) was originally selected as a specific bacterial target, but a human homologue, the inhibition of which causes cell death, was recently discovered. We developed a dual-screening strategy for selecting highly effective compounds with low inhibition effect against human PDF. We selected a new scaffold in vitro that discriminated between human and bacterial PDFs. Analyses of structure-activity relationships identified potent antibiotics such as 2-(5-bromo-1H-indol-3-yl)-N-hydroxyacetamide (6b) with the same mode of action in vivo as previously identified PDF inhibitors but without the apoptotic effects of these inhibitors in human cells.

Dates et versions

hal-00123257 , version 1 (09-01-2007)

Identifiants

Citer

Adrien Boularot, Carmela Giglione, Sylvain Petit, Yann Duroc, Rodolphe Alves de Sousa, et al.. Discovery and Refinement of a New Structural Class of Potent Peptide Deformylase Inhibitors.. Journal of Medicinal Chemistry, 2007, 50 (1), pp.10-20. ⟨10.1021/jm060910c⟩. ⟨hal-00123257⟩
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