Antileishmanial activity of 3,4,5-trisubstituted isoxazoles by interaction with Leishmania amazonensis plasma membrane

Abstract

The isoxazole core has been identified as an essential privileged structure in discovering new and potent leishmanicidal agents. Thus, the present study reports the in vitro activity of a series of thirty-five 3,4,5-trisubstituted isoxazole derivatives against the promastigote form of L. amazonensis. Cytotoxicity against macrophages, hemolysis activity, and the effect on the parasite membrane were also evaluated. The results show that eight compounds exhibited potent antileishmanial activity (IC50 < 20 μM). The compounds 2e and 3de, the most active of the series, caused a remarkable change in the fluidity of the parasite's membrane and exhibited low toxicity for mammalian cells.