1. In Vivo Antileishmanial Effect of 3,5-Diaryl-isoxazole Analogues Based on Veraguensin, Grandisin, and Machilin G: A Glance at a Preclinical Study.
- Author
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das Neves AR, Carvalho DB, Silva F, Rosalem RF, Pelizaro BI, Castilho PF, Oliveira KMP, Cassemiro NS, Pessatto LR, Paredes-Gamero EJ, Piranda EM, Silva DB, Arruda CCP, and Baroni ACM
- Subjects
- Animals, Mice, Isoxazoles pharmacology, Mice, Inbred BALB C, Lignans pharmacology, Leishmania, Leishmaniasis, Cutaneous drug therapy, Leishmaniasis, Cutaneous pathology, Antiprotozoal Agents pharmacology
- Abstract
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 .
- Published
- 2023
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