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We described here our results on the use of thiourea as a ligand in the copper catalysed azide-alkyne cycloaddition (CuAAC) of 2-azidobenzaldehyde with alkynes. Reactions were performed reacting 2-azidobenzaldehyde with a range of terminal alkynes using 10 mol % of copper iodide as a catalyst, 20 mol % of thiourea as a ligand, triethylamine as base, DMSO as solvent at 100 °C under nitrogen atmosphere. The corresponding 2-(1H-1,2,3-triazoyl)-benzaldehydes (2-TBH) were obtained in moderated to excellent yields and according our experiments, the use of thiourea decreases the formation of side products. The obtained compounds were screened for their binding affinity with multiple therapeutic targets of AD by molecular docking: β-secretase (BACE), glycogen synthase kinase (GSK-3β) and acetylcholinesterase (AChE). The three compounds with highest affinity, 5 a (2-(4-phenyl-1H-1,2,3-triazol-1-yl)benzaldehyde), 5 b (2-(4-(p-tolyl)-1H-1,2,3-triazol-1-yl)benzaldehyde), and 5 d (2-(4-(4-(tert-butyl)phenyl)-1H-1,2,3-triazol-1-yl)benzaldehyde) were selected and evaluated on its antioxidant effect, in view of select the most promising one to perform the in vivo validation. Due the antioxidant potential ally to the affinity with BACE, GSK-3β and AChE, compound 5 b was evaluated in a mouse model of AD induced by intracerebroventricular injection of streptozotocin (STZ). Our results indicate that 5 b (1 mg/kg) treatment during 20 days is able to reverse the cognitive and memory impairment induced by STZ trough the modulation of AChE activity, amyloid cascade and GSK-3β expression.

We describe herein our results on the synthesis, antioxidant properties and chemical diversification of phenylselanyl-1H-1,2,3-triazole-4-carbonitriles. These compounds were synthesized in high yields by the reaction of azidophenyl phenylselenides with a range of α-keto nitriles, using DMSO as the solvent in the presence of a catalytic amount of Et2NH (1 mol%). The synthesized compounds were screened for their in vitro antioxidant activity and 5-phenyl-1-(2-(phenylselanyl)phenyl)-1H-1,2,3-triazole-4-carbonitrile (3a) exhibited the highest antioxidant effect. In addition, the obtained triazoyl carbonitriles were readily transformed into more complex products via a cycloaddition protocol with NaN3, affording bifunctional hybrids containing triazole and tetrazole systems in good to excellent yields.