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Assessment of the Activity of Nitroisoxazole Derivatives against . | LitMetric

Assessment of the Activity of Nitroisoxazole Derivatives against .

Molecules

Programa de Farmacología Molecular y Clínica, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Av. Independencia 1027, Independencia 8380453, Chile.

Published: June 2024

AI Article Synopsis

Article Abstract

The development of new compounds to treat Chagas disease is imperative due to the adverse effects of current drugs and their low efficacy in the chronic phase. This study aims to investigate nitroisoxazole derivatives that produce oxidative stress while modifying the compounds' lipophilicity, affecting their ability to fight trypanosomes. The results indicate that these compounds are more effective against the epimastigote form of , with a 52 ± 4% trypanocidal effect for compound . However, they are less effective against the trypomastigote form, with a 15 ± 3% trypanocidal effect. Additionally, compound interacts with a higher number of amino acid residues within the active site of the enzyme cruzipain. Furthermore, it was also found that the presence of a nitro group allows for the generation of free radicals; likewise, the large size of the compound enables increased interaction with aminoacidic residues in the active site of cruzipain, contributing to trypanocidal activity. This activity depends on the size and lipophilicity of the compounds. The study recommends exploring new compounds based on the nitroisoxazole skeleton, with larger substituents and lipophilicity to enhance their trypanocidal activity.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11207111PMC
http://dx.doi.org/10.3390/molecules29122762DOI Listing

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