RESUMEN
In this study we report the synthesis, characterization, biological evaluation, and druglikeness assessment of a series of 20 novel isoxazolyl-sulfonamides, obtained by a four-step synthetic route. The compounds had their activity against Trypanosoma cruzi, Leishmania amazonensis, Herpes Simplex Virus type 1 and cytotoxicity evaluated in phenotypic assays. All compounds have drug-like properties, showed low cytotoxicity and were promising regarding all other biological activities reported herein, especially the inhibitory activity against T. cruzi. The compounds 8 and 16 showed significant potency and selectivity against T. cruzi (GI50â¯=â¯14.3⯵M, SIâ¯>â¯34.8 and GI50â¯=â¯11.6⯵M, SIâ¯=â¯29.1, respectively). These values, close to the values of the reference drug benznidazole (GI50â¯=â¯10.2⯵M), suggest that compounds 8 and 16 represent promising candidates for further pre-clinical development targeting Chagas disease.