Ultrasonic-assisted synthesis of 1,4-disubstituted 1,2,3-triazoles via various terminal acetylenes and azide and their quorum sensing inhibition.

An efficient synthesis of 1,4-disubstituted 1,2,3-triazole derivatives was studied. 1,4-Disubstituted 1,2,3-triazoles containing isoxazole and thymidine structures were synthesized in 84-96% yields starting from various terminal isoxazole ether alkynes and β-thymidine azide derivatives via a 1,3-dispolar cycloaddition using copper acetate, sodium ascorbate as the catalyst under ultrasonic assisted condition. All the target compounds were characterized by HRMS, FT-IR, 1 H NMR and 13 C NMR spectroscopy. Furthermore, the quorum sensing inhibitory activities of synthesized compounds were evaluated with Chromobacterium violaceum (C. Violaceum CV026) based on their inhibition of violacein production, with compound C10 -HSL as a positive control. The compounds 8a, 8c and 8f exhibited considerable levels of inhibitory activity against violacein production, and IC50 values were 217±19, 223±20 and 42.8±4.5μM, respectively, which highlighted the potential of these compounds as lead structures for further research towards the development of novel QS inhibitors.