Synthesis,antimicrobial activity and physico-chemical properties of some n-alkyldimethylbenzylammonium halides

Quaternary ammonium salts (chloride, bromide and iodide; QUATs) with n-alkyl chain lengths between C8 and C18 have been synthesized under optimized experimental conditions. These compounds were tested in vitro for antimicrobial activity against representative bacterial strains (Staphylococcus aureus CIP 4.83, Enterococcus hirae CIP 5855, Pseudomonas aeruginosa CIP 82118, Escherichia coli CIP 53126, Mycobacterium smegmatis CIP 7326) and fungal species (Aspergillus niger ATCC 16404, Candida albicans IP 118079, Trichophyton interdigitale IP 146583). While these compounds showed moderate antifungal activity, several of them (particularly C14-I−) may be considered as highly potential antibacterial agents against S. aureus, E. hirae and E. coli with MIC values lower than that of commercial benzalkonium chloride and ciprofloxacin used as standards. The relationship between the lipophilicity and the antibacterial activity of the tested QUATs was quantified by a multiple linear regression method

Impairment of Pseudomonas aeruginosa Biofilm Resistance to Antibiotics by Combining the Drugs with a New Quorum-Sensing Inhibitor.

Pseudomonas aeruginosa plays an important role in chronic lung infections among patients with cystic fibrosis (CF) through its ability to form antibiotic-resistant biofilms. In P. aeruginosa, biofilm development and the production of several virulence factors are mainly regulated by the rhl and las quorum-sensing (QS) systems, which are controlled by two N-acyl-homoserine lactone signal molecules. In a previous study, we discovered an original QS inhibitor, N-(2-pyrimidyl)butanamide, called C11, based on the structure of C4-homoserine lactone, and found that it is able to significantly inhibit P. aeruginosa biofilm formation. However, recent data indicate that P. aeruginosa grows under anaerobic conditions and forms biofilms in the lungs of CF patients that are denser and more robust than those formed under aerobic conditions. Our confocal microscopy observations of P. aeruginosa biofilms developed under aerobic and anaerobic conditions confirmed that the biofilms formed under these two conditions have radically different architectures. C11 showed significant dose-dependent antibiofilm activity on biofilms grown under both aerobic and anaerobic conditions, with a greater inhibitory effect being seen under conditions of anaerobiosis. Gene expression analyses performed by quantitative reverse transcriptase PCR showed that C11 led to the significant downregulation of rhl QS regulatory genes but also to the downregulation of both las QS regulatory genes and QS system-regulated virulence genes, rhlA and lasB. Furthermore, the activity of C11 in combination with antibiotics against P. aeruginosa biofilms was tested, and synergistic antibiofilm activity between C11 and ciprofloxacin, tobramycin, and colistin was obtained under both aerobic and anaerobic conditions. This study demonstrates that C11 may increase the efficacy of treatments for P. aeruginosa infections by increasing the susceptibility of biofilms to antibiotics and by attenuating the pathogenicity of the bacterium

Expression of pyrrothineN-acyltransferase activities inSaccharothrix algeriensisNRRL B-24137: new insights into dithiolopyrrolone antibiotic biosynthetic pathway

The hypothetical dithiolopyrrolone biosynthetic pathway includes a final step of pyrrothine nucleus acylation. The presence of an enzymatic activity catalysing this reaction was investigated in Saccharothrix algeriensis NRRL B‐24137. To understand the effect exerted by organic acids on the level of dithiolopyrrolone production, their influence on enzymatic expression was studied. Methods and Results: The transfer of acetyl‐CoA or benzoyl‐CoA on pyrrothine was assayed in the cell‐free extract of Sa. algeriensis NRRL B‐24137. This study reports the presence of an enzymatic activity catalysing this reaction that was identified as either pyrrothine N‐acetyltransferase or N‐benzoyltransferase. The stimulation of benzoyl‐pyrrothine (BEP) production by addition of benzoic acid at 1·25 mmol l−1 into the culture medium was demonstrated, and results showed that under the same conditions of growth, pyrrothine N‐benzoyltransferase specific activity was doubled. This study shows that BEP production is enhanced in the presence of benzoic acid partly because of an induction of pyrrothine N‐benzoyltransferase.

Yield enhancement strategy of dithiolopyrrolone from Saccharothrix algeriensis by aliphatic alcohols supplementation

Description of the relationship between protein structure and function remains a primary focus in molecular biology, biochemistry, protein engineering and bioelectronics. Moreover, the investigation of the protein conformational changes after adhesion and dehydration is of importance to tackle problems related to the interaction of proteins with solid surfaces. In this paper the conformational changes of wild-type Discosoma recombinant red fluorescent proteins (DsRed) adhered on silver nanoparticles (AgNPs)-based nanocomposites are explored via surface-enhanced Raman scattering (SERS). Originality in the present approach is to work on dehydrated DsRed thin protein layers in link with natural conditions during drying. To enable the SERS effect, plasmonic substrates consisting of a single layer of AgNPs encapsulated by an ultra-thin silica cover layer were elaborated by plasma process. The achieved enhancement of the electromagnetic field in the vicinity of the AgNPs is as high as 105. This very strong enhancement factor allowed detecting Raman signals from discontinuous layers of DsRed issued from solution with protein concentration of only 80 nM. Three different conformations of the DsRed proteins after adhesion and dehydration on the plasmonic substrates were identified. It was found that the DsRed chromophore structure of the adsorbed proteins undergoes optically assisted chemical transformations when interacting with the optical beam, which leads to reversible transitions between the three different conformations. The proposed time-evolution scenario endorses the dynamical character of the relationship between protein structure and function. It also confirms that the conformational changes of proteins with strong internal coherence, like DsRed proteins, are reversible

Synthesis and evaluation of chromone-2-carboxamide derivatives as cytotoxic agents and 5-lipoxygenase inhibitors

In the present study, we prepared a series of 21 chromone carboxamide derivatives bearing diverse amide side chains. Their potency to inhibit the proliferation of breast (MCF-7), ovarian (OVCAR and IGROV), and colon (HCT-116) cancer cell lines, was evaluated in vitro using the MTT assay. Among these compounds, 13 showed promising cytotoxic activity against at least one cancer cell line with IC50 in the range 0.9–10 μM. Our compounds were also screened for their anti-inflammatory activity as putative inhibitors of 5-lipoxygenase. Structure-activity relationships studies on our chromone carboxamide derivatives revealed that the presence of a 6-fluoro substituent on the chromone nucleus (R1) or propyl and 3-ethylphenyl groups on the amide side chain (R2) has a positive impact on the cytotoxic activity. In terms of the anti-inflammatory activity, hydrophilic chromone carboxamide derivatives showed greater 5-lipoxygenase inhibition. The physico-chemical properties of chromone carboxamides are in accordance with the general requirements of drug development process and ligand efficiency values allow further structure optimization, with compound 4b as a lead

Foldamères biologiquement actifs (synthèse, caractérisation et applications pharmacologiques)

TOULOUSE3-BU Santé-Centrale (315552105) / SudocSudocFranceF

Formation de Biofilm à Pseudomonas aeruginosa (évaluation d'inhibiteurs potentiels du quorum sensing)

TOULOUSE3-BU Sciences (315552104) / SudocSudocFranceF