Application of nanofiber-based drug delivery systems in improving anxiolytic effect of new 1,2,3-triazolo-1,4-benzodiazepine derivatives.

Anxiety disorders are highly prevalent worldwide and can affect people of all ages, genders and backgrounds. Much efforts and resources have been directed at finding new anxiolytic agents and drug delivery systems (DDSs) especially for cancer patients to enhance targeted drug delivery, reduce drug adverse effects, and provide an analgesic effect. The aim of this study was (1) to design and develop novel nanofiber-based DDSs intended for the oral administration of new 1,2,3-triazolo-1,4-benzodiazepines derivatives, (2) to investigate the physical solid-state properties of such drug-loaded nanofibers, and (3) to gain knowledge of the anxiolytic activity of the present new benzodiazepines in rodents in vivo. The nanofibers loaded with 1,2,3-triazolo-1,4-benzodiazepine derivatives were prepared by means of electrospinning (ES). Field-emission scanning electron microscopy and attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy were used for the physicochemical characterization of nanofibers. The anxiolytic activity of new derivatives and drug-loaded nanofibers was studied with an elevated plus maze test and light-dark box test. New 1,2,3-triazolo-1,4-benzodiazepine derivatives showed a promising anxiolytic effect in mice with clear changes in behavioral reactions in both tests. The nanofiber-based DDS was found to be feasible in the oral delivery of the present benzodiazepine derivatives. The nanofibers generated by means of ES presented the diameter in a nanoscale, uniform fiber structure, capacity for drug loading, and the absence of defects. The present findings provide new insights in the drug treatment of anxiety disorders with new benzodiazepine derivatives.

Effective microwave-assisted approach to 1,2,3-triazolobenzodiazepinones via tandem Ugi reaction/catalyst-free intramolecular azide-alkyne cycloaddition.

A novel catalyst-free synthetic approach to 1,2,3-triazolobenzodiazepinones has been developed and optimized. The Ugi reaction of 2-azidobenzaldehyde, various amines, isocyanides, and acids followed by microwave-assisted intramolecular azide-alkyne cycloaddition (IAAC) gave a series of target heterocyclic compounds in moderate to excellent yields. Surprisingly, the normally required ruthenium-based catalysts were found to not affect the IAAC, only making isolation of the target compounds harder while the microwave-assisted catalyst-free conditions were effective for both terminal and non-terminal alkynes.