Os efeitos do ácido cumárico e seus análogos sobre o crescimento e a biossíntese de melanina no patógeno oportunista Cryptococcus neoformans
Data
2023-12-01
Autores
Silva, Vivian Jugni 
Orientadores
Pascon, Renata Castiglioni
Tipo
Trabalho de conclusão de curso
Título da Revista
ISSN da Revista
Título de Volume
Resumo
Cryptococcus neoformans é um fungo encapsulado patogênico oportunista causador da
criptococose. Em imunocomprometidos, como portadores de HIV, transplantados e pessoas
em tratamento quimioterápico, este fungo pode causar meningoencefalite, tendo uma alta taxa
de mortalidade dentre este grupo. O tratamento é realizado por via oral, administrando
antifúngicos de forma prolongada, em altas doses e combinando diferentes fármacos. Isso
acaba sendo prejudicial para o paciente, pois esses medicamentos podem atingir o fígado e os
rins por possuir uma toxicidade seletiva baixa. Por conta disso, fazse necessário estudos de
compostos que atuem em fatores de virulência, como a biossíntese de melanina, de forma que
potencialize os fármacos já existentes, diminuindo sua dose e tempo de uso. Dessa forma o
objetivo deste trabalho foi analisar se análogos do ácido cumárico inibem tanto o crescimento
quanto a biossíntese de melanina de C. neoformans e como eles se comportam na presença de
um fármaco usado na clínica. Foram realizados testes de concentração inibitória mínima
(CIM) de melanização e de sinergismo, avaliando cada um dos objetivos. 11 compostos foram
fornecidos pelo Prof. Dr. João Paulo Fernandes. No teste CIM, todos os compostos testados
apresentaram inibição do crescimento do patógeno a uma concentração que o próprio ácido
cumárico. Três desses compostos inibiram a síntese de melanina até nas suas concentrações
subinibitórias. E um desses compostos apresentou sinergismo com anfotericina B,
demonstrandose uma possibilidade para novos tratamentos da criptococose.
Cryptococcus neoformans is an opportunistic pathogenic encapsulated fungus that causes cryptococcosis. In immunocompromised people, such as HIV carriers, transplant recipients and people undergoing chemotherapy, this fungus can cause meningoencephalitis, with a high mortality rate among this group. Treatment is carried out orally, administering antifungals for a long time, in high doses and combining different drugs. This ends up being harmful for the patient, as these medications can reach the liver and kidneys due to their low selective toxicity. Because of this, it is necessary to study compounds that act on virulence factors, such as melanin biosynthesis, in a way that enhances existing drugs, reducing their dose and time of use. Therefore, the objective of this work was to analyze whether coumaric acid analogues inhibit both the growth and melanin biosynthesis of C. neoformans and how they behave in the presence of a drug used in the clinic. Minimum Inhibitory Concentration (MIC) melanization and synergism tests were carried out, evaluating each of the objectives. 11 compounds were provided by Prof. Dr. João Paulo Fernandes. In the MIC test, all tested compounds showed inhibition of pathogen growth at a concentration higher than coumaric acid itself. Three of these compounds inhibited melanin synthesis even at subinhibitory concentrations. And one of these compounds showed synergism with amphotericin B, demonstrating a possibility for new treatments for cryptococcosis.
Cryptococcus neoformans is an opportunistic pathogenic encapsulated fungus that causes cryptococcosis. In immunocompromised people, such as HIV carriers, transplant recipients and people undergoing chemotherapy, this fungus can cause meningoencephalitis, with a high mortality rate among this group. Treatment is carried out orally, administering antifungals for a long time, in high doses and combining different drugs. This ends up being harmful for the patient, as these medications can reach the liver and kidneys due to their low selective toxicity. Because of this, it is necessary to study compounds that act on virulence factors, such as melanin biosynthesis, in a way that enhances existing drugs, reducing their dose and time of use. Therefore, the objective of this work was to analyze whether coumaric acid analogues inhibit both the growth and melanin biosynthesis of C. neoformans and how they behave in the presence of a drug used in the clinic. Minimum Inhibitory Concentration (MIC) melanization and synergism tests were carried out, evaluating each of the objectives. 11 compounds were provided by Prof. Dr. João Paulo Fernandes. In the MIC test, all tested compounds showed inhibition of pathogen growth at a concentration higher than coumaric acid itself. Three of these compounds inhibited melanin synthesis even at subinhibitory concentrations. And one of these compounds showed synergism with amphotericin B, demonstrating a possibility for new treatments for cryptococcosis.