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

• Autor(a) principal: Dias,Maria C. F.
• Data de Publicação: 2019
• Outros Autores: Gularte,Thiago Q., Teixeira,Róbson R., Santos,Jorge A. N., Pilau,Eduardo J., Mendes,Tiago A. O., Demuner,Antônio J., Santos,Marcelo H. dos
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Journal of the Brazilian Chemical Society (Online)
• Texto Completo: http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0103-50532019000100097
• topic: elastase; serine protease; CuAAC reaction; benzophenone; 1,2,3-triazole

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.