Síntese e atividade anti-pythium insidiosum in vitro de três novos compostos triazólicos

• Ano de defesa: 2023
• Autor(a) principal: Fernandes, Carolina Martins
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• dARK ID: ark:/26339/001300000srsz
• Idioma: por
• Instituição de defesa: Universidade Federal de Santa Maria; Brasil; Bioquímica; UFSM; Programa de Pós-Graduação em Ciências Biológicas: Bioquímica Toxicológica; Centro de Ciências Naturais e Exatas
• Palavras-chave em Português: Pitiose; Azóis; Compostos triazólicos; Suscetibilidade; Toxicidade; Leucócitos humanos; Pythiosis; Azoles; Triazole compounds; Susceptibility; Toxicity; Human leukocytes; CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA
• Link de acesso: http://repositorio.ufsm.br/handle/1/31109

Pythiosis is an infectious and non-transmissible disease caused by the oomycete Pythium insidiosum, which mainly affects horses, dogs and humans. Currently, there is no effective drug treatment. Triazoles are heterocyclic compounds that have aroused considerable research interest, since several of their representatives exhibit pharmacological properties against fungi and bacteria. The present study carries out the synthesis of three new triazole compounds (C1, C2 and C3), to test their possible in vitro activities against P. insidiosum isolates and to evaluate their safety on human leukocytes. After synthesis of the triazoles via click-type reaction, the compounds were used in the susceptibility tests for P. insidiosum isolates (n = 15), were determined the minimum inhibitory concentration (MIC) and minimum oomicidal concentration (MOC). The toxicity of triazoles on leukocytes was evaluated through measurements of cell viability, morphological aspects, and endpoints of oxidative stress. Prediction of the absorption, distribution, metabolism, excretion and toxicity properties of compounds (ADMET) in silico was determined using the pkCSM platform. The new triazoles exhibited anti-Pythium insidiosum activity at similar concentration ranges. P. insidiosum isolates contained MIC and MOC from 2-64 μg/mL for C1, 2-64 μg/mL for C2, while MIC from 4-64 μg/mL and MOC 8-64 μg/mL for C3. The three compounds were not toxic to human leukocytes since they did not induce viability loss and/or morphologic changes, and did not present a pro-oxidant profile. The prediction of the ADMET properties of the compounds in silico was similar to the reference drug fluconazole. This is the first study showing new triazole compounds with anti-P. insidiosum activity at concentrations non-toxic to human leukocytes.