Optimization of the Antibacterial Spectrum and the Developability Profile of the Novel-Class Natural Product Corramycin.

Corramycin is a novel zwitterionic antibacterial peptide isolated from a culture of the myxobacterium . Though Corramycin displayed a narrow spectrum and modest MICs against sensitive bacteria, its ADMET and physchem profile as well as its high tolerability in mice along with an outstanding in vivo efficacy in an septicemia mouse model were promising and prompted us to embark on an optimization program aiming at enlarging the spectrum and at increasing the antibacterial activities by modulating membrane permeability. Scanning the peptidic moiety by the Ala-scan strategy followed by key stabilization and introduction of groups such as a primary amine or siderophore allowed us to enlarge the spectrum and increase the overall developability profile.

In vitro ion channel profile and ex vivo cardiac electrophysiology properties of the R(-) and S(+) enantiomers of hydroxychloroquine.

Hydroxychloroquine (HCQ) is a derivative of the antimalaria drug chloroquine primarily prescribed for autoimmune diseases. Recent attempts to repurpose HCQ in the treatment of corona virus disease 2019 has raised concerns because of its propensity to prolong the QT-segment on the electrocardiogram, an effect associated with increased pro-arrhythmic risk. Since chirality can affect drug pharmacological properties, we have evaluated the functional effects of the R(-) and S(+) enantiomers of HCQ on six ion channels contributing to the cardiac action potential and on electrophysiological parameters of isolated Purkinje fibers.

Influence of Chirality of Lactones on the Perception of Some Typical Fruity Notes through Perceptual Interaction Phenomena in Bordeaux Dessert Wines.

Recent studies concerning the aroma of noble rot dessert wines revealed the importance of a well-known phenomenon in perfumery, the perceptual blending, to create the perception of "overripe orange" nuances. Thus, compounds associated with both oak wood aging (3-methyl-4-octanolide and eugenol) and Botrytis cinerea development under the form of noble rot (2-nonen-4-olide and γ-nonalactone) contribute to a specific aroma of great noble rot dessert wines through perceptual interaction phenomena. This synthetic perception phenomenon was established from reconstitution, addition, and omission sensory experiments, using wine extract fractions supplemented with the volatile compounds previously mentioned.

Total Synthesis of Putative 11-epi-Lyngbouilloside Aglycon.

We report here the total synthesis of 11-epi-lyngbouilloside aglycon. Our strategy features a Boeckman-type esterification followed by a RCM to form the 14-membered ring macrolactone and a late-stage side chain introduction via a Wittig olefination. Overall, the final product was obtained in 20 steps and 2% overall yield starting from commercially available 3-methyl-but-3-enol.