A Concise Synthesis of Pyrrole-Based Drug Candidates from α-Hydroxyketones, 3-Oxobutanenitrile, and Anilines.

A simple and concise three-component synthesis of a key pyrrole framework was developed from the reaction between α-hydroxyketones, oxoacetonitriles, and anilines. The synthesis was used to obtain several pyrrole-based drug candidates, including COX-2 selective NSAID, antituberculosis lead candidates BM212, BM521, and BM533, as well as several analogues. This route has potential to obtain diverse libraries of these pyrrole candidates in a concise manner to develop optimum lead compounds.

Selective One-Pot Cascade Synthesis of N-Substituted Highly Functionalized Pyrroles from Unprotected Sugars, Primary Amines, and Oxoacetonitriles.

A one-pot, three-component cascade reaction between unprotected sugars, primary amines, and 3-oxoacetonitriles gave N-substituted 2,3,5-functionalized pyrroles or N-substituted 2,3,4-functionalized pyrroles in excellent yields and selectivities. The selectivity of the reaction was achieved by simple control of the sequence of substrate addition. The reaction showed a wide substrate scope, and various types of sugars, primary amines, and oxoacetonitriles reacted smoothly.

Selective One-Pot Multicomponent Synthesis of -Substituted 2,3,5-Functionalized 3-Cyanopyrroles via the Reaction between α-Hydroxyketones, Oxoacetonitriles, and Primary Amines.

A one-step, three-component reaction between α-hydroxyketones, oxoacetonitriles, and primary amines gives -substituted 2,3,5-functionalized 3-cyanopyrroles with complete selectivity in up to 90% isolated yields. The reaction worked on a wide substrate scope under mild reaction conditions (AcOH as a catalyst, EtOH, 70 °C, 3 h). The reaction proceeded with very high atom efficiency as water is the only molecule lost during the reaction.

A Practical Synthesis of Densely Functionalized Pyrroles via a Three-Component Cascade Reaction between Carbohydrates, Oxoacetonitriles, and Ammonium Acetate.

A practical three-component reaction between unactivated carbohydrates, oxoacetonitriles, and ammonium acetate gave densely functionalized pyrroles in 75-96% yields. Disaccharides afforded novel pyrrolo-glycosides. This metal-free, EtN-catalyzed cascade reaction proceeded with exclusive chemo-, regio-, and stereoselectivities and showed a wide substrate scope with high atom economy.

Perfluorophenylboronic acid-catalyzed direct α-stereoselective synthesis of 2-deoxygalactosides from deactivated peracetylated d-galactal.

Perfluorophenylboronic acid 1c catalyzes the direct stereoselective addition of alcohol nucleophiles to deactivated peracetylated d-galactal to give 2-deoxygalactosides in 55-88% yield with complete α-selectivity. The unprecedented results reported here also enable the synthesis of disaccharides containing the 2-deoxygalactose moiety directly from the deactivated peracetylated d-galactal. This convenient and metal-free glycosylation method works well with a wide range of alcohol nucleophiles as acceptors and tolerates a range of functional groups without the formation of the Ferrier byproduct and without the need for a large excess of nucleophiles or additives.

Robust perfluorophenylboronic acid-catalyzed stereoselective synthesis of 2,3-unsaturated -, -, - and -linked glycosides.

A convenient protocol was developed for the synthesis of 2,3-unsaturated , - and -linked glycosides (enosides) using 20 mol % perflurophenylboronic acid catalyst via Ferrier rearrangement. Using this protocol, D-glucals and L-rhamnals reacted with various , - and -nucleophiles to give a wide range of glycosides in up to 98% yields with mainly α-anomeric selectivity. The perflurophenylboronic acid successfully catalyzed a wide range of substrates (both glucals and nucleophiles) under very mild reaction conditions.

Glabridin resensitizes p-glycoprotein-overexpressing multidrug-resistant cancer cells to conventional chemotherapeutic agents.

Multidrug resistance (MDR) remains an obstacle to chemotherapy related with the overexpression of several efflux membrane proteins, and p-glycoprotein (P-gp) is the most studied among them. Thus, continuous investigational efforts are necessary to find valuable MDR reversal agents, and the flavonoid compound glabridin (GBD) seems to be a promising candidate. This study aimed to investigate the potential of GBD against MDR and explore the possible mechanisms.

Inhibition of P-Glycoprotein Mediated Efflux in Caco-2 Cells by Phytic Acid.

Phytic acid (IP6) is a natural phosphorylated inositol, which is abundantly present in most cereal grains and seeds. This study investigated the effects of IP6 regulation on P-glycoprotein (P-gp) and its potential mechanisms using in situ and in vitro models. The effective permeability of the typical P-gp substrate rhodamine 123 (R123) in colon was significantly increased from (1.

Self-nanoemulsifying drug delivery systems of myricetin: Formulation development, characterization, and in vitro and in vivo evaluation.

Despite various pharmacological effects, myricetin (Myr) shows low oral bioavailability (<10%) due to its poor solubility, which limits its applications. To address this problem, self-nanoemulsifying drug delivery systems (SNEDDS) were developed by investigating the solubility of Myr in various excipients, constructing pseudo-ternary phase diagrams, and optimizing based on droplet size and emulsification efficacy after drug loading. The obtained Myr-SNEDDS were F04 (Capryol 90/Cremophor RH 40/PEG 400 4:3:3), F08 (Capryol 90/CremophorRH40/1,2-propanediol 4:3:3), F13 (Capryol 90/Cremophor EL/Transcutol HP 4:3:3) and F15 (Capryol 90/Cremephor RH 40/Transcutol HP 2:7:1), with droplet sizes less than 200nm.

Calcium Phosphate-Reinforced Reduction-Sensitive Hyaluronic Acid Micelles for Delivering Paclitaxel in Cancer Therapy.

For addressing the dilemma of in vivo stability and antitumor effects of micellar drugs, novel organic and inorganic hybridized nanoparticle, that is, hyaluronic acid-mineralized micelles, are designed to efficiently deliver paclitaxel (PTX). The resulting micelles exhibit excellent drug loading (30.6%) and entrapment efficiency (87.

Preparation and evaluation of chitosan-based nanogels/gels for oral delivery of myricetin.

A novel nanogel/gel based on chitosan (CS) for the oral delivery of myricetin (Myr) was developed and evaluated comprehensively. The particle size of the obtained Myr-loaded CS/β-glycerol phosphate (β-GP) nanogels was in the range of 100-300nm. The rheological tests showed that the sol-gel transition happened when the nanogels were exposed to physiological temperatures, and 3D network structures of the gelatinized nanogels (gels) were confirmed by Scanning Electron Microscopy.

The effect of phytic acid on tight junctions in the human intestinal Caco-2 cell line and its mechanism.

This study investigated the effect of phytic acid (IP6), a potential absorption enhancer of flavonoid components, on tight junction (TJ) integrity in Caco-2 cell monolayers and its possible mechanisms. Transepithelial electrical resistance (TEER) across the monolayers decreased rapidly, and the flux of fluorescein sodium (a paracellular marker) increased after treating with IP6 in a concentration-dependent manner. Confocal microscopy results showed that IP6 produced a concentration-dependent attenuation in the distribution of occludin, ZO-1, and claudin-1.