Importance of the 2,6-Difluorobenzamide Motif for FtsZ Allosteric Inhibition: Insights from Conformational Analysis, Molecular Docking and Structural Modifications.

A conformational analysis and molecular docking study comparing 2,6-difluoro-3-methoxybenzamide (DFMBA) with 3-methoxybenzamide (3-MBA) has been undertaken for investigating the known increase of FtsZ inhibition related anti activity due to fluorination. For the isolated molecules, the calculations reveal that the presence of the fluorine atoms in DFMBA is responsible for its non-planarity, with a dihedral angle of -27° between the carboxamide and the aromatic ring. When interacting with the protein, the fluorinated ligand can thus more easily adopt the non-planar conformation found in reported co-crystallized complexes with FtsZ, than the non-fluorinated one.

Structural Variations in the Central Heterocyclic Scaffold of Tripartite 2,6-Difluorobenzamides: Influence on Their Antibacterial Activity against MDR .

Five series of heterocyclic tripartite 2,6-difluorobenzamides, namely 1,2,3-triazoles, 1,2,4- and 1,3,4-oxadiazoles, analogs of reported model anti-staphylococcal compounds, were prepared. The purpose was to investigate the influence of the nature of the heterocyclic central scaffold on the biological activity against three strains of including two drug-resistant ones. Among the 15 compounds of the new collection, a 3-(4--butylphenyl)-1,2,4-oxadiazole linked via a methylene group with a 2,6-difluorobenzamide moiety () exhibited a minimal inhibitory concentration between 0.

IgA Serological Response for the Diagnosis of Mycobacterium abscessus Infections in Patients with Cystic Fibrosis.

The immunoglobulin A (IgA) status of cystic fibrosis (CF) patients, presenting with or without a non-tuberculous mycobacterial (NTM) infection, has to date not been fully elucidated toward two antigenic preparations previously described. We have chosen to determine the clinical values of an IgA ELISA for the diagnosis of NTM and/or Mycobacterium abscessus infections in CF patients. One hundred and 73 sera from CF patients, comprising 33 patients with M.

Synthesis and Biological Evaluation of Benzo[]thiophene Acylhydrazones as Antimicrobial Agents against Multidrug-Resistant .

The benzo[]thiophene nucleus and the acylhydrazone functional group were combined to prepare three new series of compounds for screening against . The reaction of substituted benzo[]thiophene-2-carboxylic hydrazide and various aromatic or heteroaromatic aldehydes led to a collection of 26 final products with extensive structural diversification on the aromatic ring and on position 6 of the benzo[]thiophene nucleus. The screening lead to the identification of eight hits, including ()-6-chloro-'-(pyridin-2-ylmethylene)benzo[]thiophene-2-carbohydrazide (), a non-cytotoxic derivative showing a minimal inhibitory concentration of 4 µg/mL on three strains, among which were a reference classical strain and two clinically isolated strains resistant to methicillin and daptomycin, respectively.

Serological biomarkers for the diagnosis of Mycobacterium abscessus infections in cystic fibrosis patients.

Background: Culture conditions sometimes make it difficult to detect non-tuberculous mycobacteria (NTM), particularly Mycobacterium abscessus, an emerging cystic fibrosis (CF) pathogen. The diagnosis of NTM positive cases not detected by classical culture methods might benefit from the development of a serological assay.

Methods: As part of a diagnostic accuracy study, a total of 173 sera CF-patients, including 33 patients with M.

Evaluation of Xpert MTB/RIF Ultra performance for pulmonary tuberculosis diagnosis on smear-negative respiratory samples in a French centre.

Tuberculosis (TB) is a worldwide public health concern, including in high-resource countries with a low prevalence of TB. Xpert MTB/RIF assay was developed to improve TB and rifampicin (RIF) resistance detection, but sensitivity remains poor on smear-negative sputum. Xpert MTB/RIF Ultra assay was designed to enhance the sensitivity of TB detection in clinical samples.