The Effect of Capsaicin Derivatives on Tight-Junction Integrity and Permeability of Madin-Darby Canine Kidney Cells

Capsaicin is known to interfere with tight junctions (TJs) of epithelial cells and therefore to enhance paracellular permeability of poorly absorbable drugs. However, due to its low water solubility, pungency, and cytotoxicity, its pharmacologic use is limited. In this study, we investigated the effect of capsaicin derivatives of synthetic (e.g., 10-hydroxy-N-(4-hydroxy-3-methoxybenzyl)decanamide, etc.) and natural (olvanil and dihydrocapsaicin) origin on Madin-Darby Canine Kidney–C7 cells. Impedance spectroscopy was used to determine the transepithelial electrical resistance and the capacitance. Permeability assays with fluorescein isothiocyanate–dextran were carried out to evaluate the impact on cell permeability. The results show that lipophilicity could play an important role for the interference with TJ and that the mechanism is independent from the ion channel TRPV-1 and hence on the flux of calcium into the cells. In summary, we synthesized 4 derivatives of capsaicin of lower lipophilicity and compared their properties with other well-known vanilloids. We show that these compounds are able to enhance the permeability of a hydrophilic macromolecule, by opening the TJ for a shorter time than capsaicin. This behavior is dependent on the lipophilicity of the molecule. Understanding of these phenomena may lead to better control of administration of therapeutic molecules

2-Deoxyglycosyl 3-benzoylpropionates as novel donors for the direct and stereoselective synthesis of 2-deoxy-glycosides

Lewis acid mediated stereoselective synthesis of 2-deoxy-O-glycosides has been demonstrated using 2-deoxyglycosyl 3-benzoylpropionates as novel glycosyl donors. These newly developed donors are easily synthesized from simple glycals, are stable at room temperature and react with ease to provide products with high stereoselectivity. These donors can be successfully utilized with all types of acceptors (primary, secondary and tertiary alcohols) for the synthesis of 2-deoxy-glycosides. Additionally, these newly developed glycosyl donors are also efficient for the synthesis of trisaccharides

Diversity-Oriented Synthetic Endeavors of Newly Designed Ferrier and Ferrier-Nicholas Systems Derived from 1-C-Alkynyl-2-deoxy-2-C-Methylene Pyranosides

Novel pyranose derivatives that display Ferrier- and Ferrier-Nicholas-like reactivity have been designed. These systems: 1-C-alkynyl-2-deoxy-2-C-methylene pyranosides (Ferrier), and their corresponding dicobalthexacarbonyl alkenyl derivatives (Ferrier-Nicholas), which can be accessed by a concise synthetic route from commercially available tri-O-acetyl-d-glucal, allow the incorporation of two nucleophiles (at positions C-3 and C-2′) in the pyranose ring. The study of these systems has resulted in the discovery of novel reaction patterns that allow, among others, access to open-chain derivatives, branched pyranosides, 1,6-anhydro derivatives and, when reacting with indole, access to a new family of tetracyclic indole-containing carbohydrate derivatives, namely, cyclohepta[b]indole-fused glycals. The latter are, most likely, formed by a bis Ferrier-type rearrangement followed by an unusual intramolecular 7-endo-dig Friedel–Crafts alkenylation of one of the indole moieties by the C-1 alkyne.Financial support from Ministerio de Economia y Competitividad (MINECO, Spain), grant CTQ2015-66702-R (MINECO/FEDER), is gratefully acknowledged. Silvia Miranda thanks the Ministerio de Economia y Competitividad for a predoctoral fellowship.Peer Reviewe