Synthesis of Novel Polyhydroxylated Tetrahydropyranopyrroles

The stereoselective access to original polyhydroxylated tetrahydropyranopyrroles is described. The key steps involve an ­inverse-demand Diels-Alder reaction and a ring contraction of a ­pyridazine heterocycle

Synthesis of Polyhydroxylated Pyrano-Pyrrole Derivatives from Carbohydrate Precursors

The efficient synthesis of novel polyhydroxy‐tetrahydropyrano‐pyrroles from acetylenic carbohydrate precursors in three to four steps is described. The methodology involves, as key steps, the ring contraction of pyridazine intermediates obtained by an inverse‐demand Diels–Alder reaction and subsequent intramolecular lactonization

Exploration of Long-Chain Vitamin E Metabolites for the Discovery of a Highly Potent, Orally Effective, and Metabolically Stable 5-LOX Inhibitor that Limits Inflammation.

Endogenous long-chain metabolites of vitamin E (LCMs) mediate immune functions by targeting 5-lipoxygenase (5-LOX) and increasing the systemic concentrations of resolvin E3, a specialized proresolving lipid mediator. SAR studies on semisynthesized analogues highlight α-amplexichromanol (27a), which allosterically inhibits 5-LOX, being considerably more potent than endogenous LCMs in human primary immune cells and blood. Other enzymes within lipid mediator biosynthesis were not substantially inhibited, except for microsomal prostaglandin E2 synthase-1. Compound 27a is metabolized by sulfation and β-oxidation in human liver-on-chips and exhibits superior metabolic stability in mice over LCMs. Pharmacokinetic studies show distribution of 27a from plasma to the inflamed peritoneal cavity and lung. In parallel, 5-LOX-derived leukotriene levels decrease, and the inflammatory reaction is suppressed in reconstructed human epidermis, murine peritonitis, and experimental asthma in mice. Our study highlights 27a as an orally active, LCM-inspired drug candidate that limits inflammation with superior potency and metabolic stability to the endogenous lead

Synthesis of new selected analogues of the proapoptotic and anticancer molecule HA 14-1.

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Design, synthesis and biological evaluation of fluorescent ligands for MT1 and/or MT2 melatonin receptors

Design, synthesis and biological evaluation of fluorescent ligands for MT1 and/or MT2 melatonin receptors. 24. Conference of the Groupement des Pharmacochimistes de l'Arc Atlantique (GP2A

Mitochondrial targeting by use of lipid nanocapsules loaded with SV30, an analogue of the small-molecule Bcl-2 inhibitor HA14-1.

International audienceTaking advantage from the development of SV30, a new analogue of the pro-apoptotic molecule HA14-1, the aim of this study was to functionally evaluate SV30 and to develop safe nanocarriers for its administration. By using an inversion phase process, 57nm organic solvent-free lipid nanocapsules loaded with SV30 (SV30-LNCs) were formulated. Biological performance of SV30 and SV30-LNCs were evaluated on F98 cells that express Bax and Bcl-2, through survival assays, HPLC, flow cytometry, confocal microscopy and spectral imaging. We observed that SV30 alone or in combination with paclitaxel, etoposide or beam radiation could trigger cell death in a similar fashion to HA14-1. Although partially blocked by Z-VAD-fmk, this effect was coincident to caspase-3 activation. Hence, we established that SV30-LNCs improved SV30 biological activity together with a potentiation of the mitochondrial membrane potential decrease. Interestingly, flow cytometry and confocal analysis indicated that SV30 itself conferred to LNCs improved mitochondrial targeting skills that may present a great interest toward the development of mitochondria targeted nanomedicines

MixONat: Assistance aux analyses déréplicatives par RMN-13C

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