Investigação da atividade antifúngica de ésteres do ácido pirazinóico
Data
2016-11-22
Autores
Silva, Rafael Augusto Mantovani 
Orientadores
Fernandes, João Paulo dos Santos
Tipo
Trabalho de conclusão de curso
Título da Revista
ISSN da Revista
Título de Volume
Resumo
Estima-se que cerca de um bilhão de pessoas, de todas as partes do mundo, sofram de
infecções fúngicas. Apesar do elevado número de pacientes diagnosticados com infecções
fúngicas, há um número limitado de fármacos disponíveis para o tratamento destes pacientes.
O reposicionamento de fármacos possibilita a utilização de um fármaco já extensamente
estudado, em outra indicação que não a original. Os ésteres do ácido pirazinóico possuem
atividade contra micobactérias, possivelmente por uma melhor penetração na parede celular
deste organismo que o ácido pirazinóico (POA). O trabalho teve como objetivo sintetizar
ésteres do ácido pirazinóico através de reações de alcoólise do cloreto de pirazinoíla em etapa
única e avaliar a atividade antifúngica destes análogos de POA em espécies de Candida (C.
albicans, C. tropicalis e C. parapsilosis), pois apresentam uma prevalência de infecções alta
em seres humanos e, assim, um impacto socioeconômico importante. Quatro ésteres
pirazinoatos (metila, etila, isopropila e butila) foram sintetizados com rendimentos entre 20 e
80%, e adequadamente caracterizados por RMN. Os resultados mostraram que alguns ésteres
do ácido pirazinóico apresentaram atividade antifúngica na escala de micromolar,
apresentando valores de IC50 entre 165-280 µM, em especial, os compostos pirazinoato de
etila e pirazinoato de isopropila que apresentaram as melhores atividades antifúngica. A
espécie mais sensível aos compostos foi C. albicans, enquanto a mais resistente, C. tropicalis.
Conclui-se que POA e seus ésteres constituem-se como novos protótipos para o
desenvolvimento de moléculas mais ativas contra fungos
It is estimated that about 1 billion people, from all over the world, suffer from fungal infections. Despite the high number of patients diagnosed with fungal infections, there are a limited number of drugs available for the treatment of these patients. The repositioning of drugs allows the use of a drug already extensively studied, in another indication than the original one. The esters of pyrazinoic acid have activity against mycobacteria, possibly through a better penetration into the cell wall of this organism than pyrazinoic acid (POA). The aim of this work was to synthesize esters of pyrazinoic acid through alcoholization reactions of pyrazinoyl chloride in a single step and to evaluate the antifungal activity of these POA analogues in Candida species (C. albicans, C. tropicalis and C. parapsilosis) as they present a high prevalence of infections in humans and, thus, a significant socioeconomic impact. Four pyrazinoate esters (methyl, ethyl, isopropyl and butyl) were synthesized in yields of between 20 and 80%, and suitably characterized by NMR. The results showed that some esters of pyrazinoic acid showed antifungal activity on the micromolar scale, with IC 50 values between 165-280 μM, especially the compounds pyrazinoate of ethyl and pyrazinoate of isopropyl which presented the best antifungal activities. The most sensitive species to the compounds was C. albicans, whereas the more resistant species, C. tropicalis. It is concluded that POA and its esters constitute as new prototypes for the development of molecules more active against fungi.
It is estimated that about 1 billion people, from all over the world, suffer from fungal infections. Despite the high number of patients diagnosed with fungal infections, there are a limited number of drugs available for the treatment of these patients. The repositioning of drugs allows the use of a drug already extensively studied, in another indication than the original one. The esters of pyrazinoic acid have activity against mycobacteria, possibly through a better penetration into the cell wall of this organism than pyrazinoic acid (POA). The aim of this work was to synthesize esters of pyrazinoic acid through alcoholization reactions of pyrazinoyl chloride in a single step and to evaluate the antifungal activity of these POA analogues in Candida species (C. albicans, C. tropicalis and C. parapsilosis) as they present a high prevalence of infections in humans and, thus, a significant socioeconomic impact. Four pyrazinoate esters (methyl, ethyl, isopropyl and butyl) were synthesized in yields of between 20 and 80%, and suitably characterized by NMR. The results showed that some esters of pyrazinoic acid showed antifungal activity on the micromolar scale, with IC 50 values between 165-280 μM, especially the compounds pyrazinoate of ethyl and pyrazinoate of isopropyl which presented the best antifungal activities. The most sensitive species to the compounds was C. albicans, whereas the more resistant species, C. tropicalis. It is concluded that POA and its esters constitute as new prototypes for the development of molecules more active against fungi.