Synthesis of Novel Benzylic 1,2,3-triazole-4-carboxamides and their in vitro Activity Against Clinically Common Fungal Species

Abstract. A library of novel benzylic 1,2,3-triazole-4-carboxamides (3a-m) were obtained with acceptable yields via a one-pot procedure. The series of compounds was screened for fungicidal activity and evaluated in vitro against four filamentous fungi and four Candida species. The former consisted of Aspergillus fumigatus, Trichosporon cutaneum, Rhizopus oryzae and Mucor hiemalis, and the latter C. krusei, C. albicans, C. utilis and C. glabrata. According to the in vitro assays, 3d and 3e were the most efficient fungicidal agents (of all the test compounds) against R. oryzae, even better than the reference drug (itraconazole). Thus, 3d and 3e represent important scaffolds that can be modified to increase antifungal activity. Additionally, they are candidates for complementary studies on the inhibition of clinical infections produced by Rhizopus spp. strains.   Resumen. Se obtuvo una libreria de nuevos bencil 1,2,3-triazoles-4-carboxamidas (3a-m) con rendimientos aceptables mediante un procedimiento one-pot. La serie de compuestos se selecciono para determinar la actividad fungicida llevando a cabo una evaluacion in vitro contra cuatro hongos filamentosos y cuatro especies de Candida. Los primeros consistieron en Aspergillus fumigatus, Trichosporon cutaneum, Rhizopus oryzae y Mucor hiemalis, mientras que para las segundas especies, esta fueron C. krusei, C. albicans, C. utilis y C. glabrata. Segun los ensayos in vitro, 3d y 3e fueron los agentes fungicidas mas eficaces (de todos los compuestos de prueba) contra R. oryzae, incluso mejores que el farmaco de referencia (itraconazol). Por tanto, 3d y 3e representan importantes nucleos que podrian modificarse para aumentar la actividad antifungica, siendo excelentes candidatos para estudios complementarios sobre la inhibicion de infecciones clinicas producidas por Rhizopus spp.