Work

Leishmanicidal and trypanocidal potential of ß,γ-unsaturated carboxylic acid synthetic derivatives

Year: 2025

Type: article

Abstract: Leishmaniasis and Chagas disease are parasitic infections with limited treatment options due to drug toxicity and rising resistance. Leishmaniasis, caused by Leishmania spp., often manifests in a cutaneous form and is treated with drugs like amphotericin B and miltefosine, which can cause severe side effects. Chagas disease, caused by Trypanosoma cruzi , is endemic in the Americas and classified by the WHO as a neglected tropical disease. Existing treatments are effective mainly in the acute phase but have significant limitations. In search of new therapies, this study explored diversity-oriented synthesis to generate a library of β,γ-unsaturated carboxylic acid derivatives. From 23 synthesized compounds –12 reported for the first time– several showed promising antiparasitic activity. Four compounds were effective against Leishmania amazonensis , with three also targeting the amastigote form. Two compounds showed activity against Trypanosoma cruzi , outperforming reference drugs in selectivity. Signs of parasite apoptosis, including mitochondrial damage and ROS accumulation, suggest strong therapeutic potential for these derivatives. • 23 β,γ-unsaturated carboxylic acid derivatives were synthesized and screened. • Six compounds showed selective leishmanicidal or trypanocidal activity. • SET-12 outperformed miltefosine in selectivity against Leishmania amastigotes. • ROS accumulation and mitochondrial dysfunction suggest apoptosis-like cell death.

Source: European Journal of Medicinal Chemistry

DOI: 10.1016/j.ejmech.2025.118390