Antileishmanial activity, cytotoxicity, and immunomodulatory effects of a naphthoquinone derivative

This study evaluated the antileishmanial activity, toxicity, and immunomodulatory effects of the synthetic compound IM4, derived from β-lapachone. In promastigote forms, IM4 showed IC₅₀ values of 4.82 ± 0.11 μg/mL for L. infantum and 15.76 ± 0.67 μg/mL for L. amazonensis. In murine macrophages, the cytotoxicity of IM4 was CC₅₀ 125.90 ± 0.13 μg/mL. Hemolysis assays showed no significant hemolysis, with erythrocyte viability remaining above 80% even at the highest concentration tested. In an in vivo model using Tenebrio molitor larvae, IM4 showed greater toxicity at the higher concentration (60 mg/kg), with 50% survival. Treatment with IM4 reduced infection and infectivity by L. amazonensis and L. infantum in murine macrophages. IM4 did not induce a significant increase in nitrite production in uninfected or infected macrophages. This compound also enhanced phagocytic capacity and lysosomal volume in murine macrophages, suggesting an immunomodulatory effect. These results reinforce the notion that bioactive compounds have significant potential for drug development, with IM4 serving as a notable example. This supports continued studies to elucidate its mechanism of action and assess its efficacy as a therapeutic agent against leishmaniasis.