Synthesis of 1,2,3-Triazole Derivatives of 4,4'-Dihydroxybenzophenone and Evaluation of Their Elastase Inhibitory Activity

• Autor(a) principal: Maria Cecília Fernandes Dias
• Data de Publicação: 2018
• Outros Autores: Thiago Gularte, Róbson Teixeira, Jorge Santos, Eduardo Pilau, Tiago Mendes, Antônio Demuner, Marcelo Dos Santos
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional da UFMG
• Texto Completo: http://hdl.handle.net/1843/41443
• topic: Elastase; Serina protease; Reação CuAAC; Benzofenona; 1,2,3-triazol

The present investigation describes the synthesis of a series of novel triazole derivatives from 4,4’-dihydroxybenzophenone along with their elastase inhibitory activity. The 1,2,3-triazoles were obtained via the copper(I)-catalyzed azide-alkyne cycloaddition reaction (CuAAC), also known as click reaction, between bis(4-(prop-2-yn-1-yloxy))benzophenone and several benzyl azides. It was found that five derivatives exhibited significant inhibitory effects, presenting half maximal inhibitory concentration (IC50) values in the range of 16.6 to 72.1 µM. The most active compound, namely bis(4-(1-(4-iodobenzyl)-1H-1,2,3-triazol-4-yl)methoxy)benzophenone (IC50 = 16.6 ± 1.9 µM), was found to bind to elastase with the inhibition constant (Ki ) of 11.12 µM, thereby illustrating competitive inhibitory behavior. Further, docking investigations provided insights on the possible binding mode of the most active compound with the elastase.