New treatment approaches targeting cutaneous leishmaniasis
(CL)
are required since conventional drugs exhibit limitations due to their
several adverse effects and toxicity. In this study, we aimed to evaluate
the in vivo intralesional treatment efficacy of five isoxazole derivatives
previously synthesized and effective in vitro against intracellular
amastigote forms of Leishmania (L.) amazonensis. Among the tested analogues, 7 exhibited relevant in
vivo therapeutic effects. The in silico predictions provided interesting
information about the toxicity, suggesting the safety of analogue 7. Experiments performed with Salmonella typhimurium strains (TA98, TA100, and TA102) showed a non-mutagenicity profile
of 7. The treatment of Leishmania-infected
BALB/c mice with isoxazole 7 showed remarkably smaller
CL lesions and decreased the parasitism (by 98.4%) compared to the
control group. Hence, analogue 7 is a promising drug
candidate and alternative treatment for CL caused by L. amazonensis.
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