In Vivo Antileishmanial Effect of 3,5-Diaryl-isoxazole Analogues Based on Veraguensin, Grandisin, and Machilin G: A Glance at a Preclinical Study

• DOI: 10.1021/acsinfecdis.3c00090
• Publication Date: 2023-04-27T15:33:31Z
• Authors: Amarith R. das Neves; Diego B. Carvalho; Fernanda Silva; Rafael F. Rosalem; Bruno I. Pelizaro; Pamella F. Castilho; Kelly M. P. Oliveira; Nadla S. Cassemiro; Lucas R. Pessatto; Edgar J. Paredes-...; Eliane M. Piranda; Denise B. Silva; Carla C. P. Arruda; Adriano C. M. Baroni
• Keywords: Isoxazole; Amastigote

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 evaluate the in vivo intralesional efficacy of five isoxazole derivatives previously synthesized effective vitro against intracellular amastigote forms Leishmania (L.) amazonensis. Among tested analogues, 7 exhibited relevant therapeutic effects. The silico predictions provided interesting information about toxicity, suggesting safety analogue 7. Experiments performed with Salmonella typhimurium strains (TA98, TA100, TA102) showed a non-mutagenicity profile Leishmania-infected BALB/c mice remarkably smaller CL lesions decreased parasitism (by 98.4%) compared control group. Hence, is promising drug candidate alternative for caused by L.