Discovery and refinement of a new structural class of potent peptide deformylase inhibitors.

Article Details

Citation

Copy to clipboard

Boularot A, Giglione C, Petit S, Duroc Y, Alves de Sousa R, Larue V, Cresteil T, Dardel F, Artaud I, Meinnel T

Discovery and refinement of a new structural class of potent peptide deformylase inhibitors.

J Med Chem. 2007 Jan 11;50(1):10-20.

PubMed ID

17201406 [ View in PubMed

]

Abstract

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.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
2-[(Formyl-Hydroxy-Amino)-Methyl]-Heptanoic Acid [1-(2-Hydroxymethyl-Pyrrolidine-1-Carbonyl)-2-Methyl-Propyl]-Amide	Peptide deformylase, mitochondrial	IC 50 (nM)	600	N/A	N/A	Details