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Evaluation of the antifungal potential of natural marine compounds
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As infeções fúngicas invasivas representam uma ameaça à saúde global. Estas infeções
estão associadas a altas taxas de mortalidade e morbidade, em parte devido à ineficácia
dos fármacos antifúngicos disponíveis. Nos últimos anos, o aumento de infeções deste
tipo, resistentes aos atuais antifúngicos tem vindo a agravar este cenário e tornou
prioritário o desenvolvimento de novos fármacos mais eficazes. A biodiversidade
marinha, ainda pouco explorada, constitui uma fonte ilimitada de novos metabolitos com
potencial aplicação clínica que pode acelerar a descoberta de novos fármacos. O fraco
investimento no desenvolvimento de novos medicamentos, juntamente com a emergência
de espécies resistentes aos antifúngicos atuais, tem aumentado o impacto negativo destas
doenças nos pacientes e sistemas de saúde.
Neste trabalho, o potencial antifúngico de duas bibliotecas de 65 e 44 extratos marinhos
recolhidos na Península de Yucatan, México, foi testado utilizando espécies de Candida,
leveduras oportunistas que podem causar infeções fúngicas invasivas nosocomiais. Foram
identificados quatro extratos marinhos com atividade antifúngica promissora. Todos eles
tinham atividade fungicida e, pelo menos dois, eram minimamente tóxicos in vitro. O
fracionamento destes extratos com recurso a ensaios bioguiados aliados a metodologias
bioquímicas e biofísicas permitiu a purificação parcial dos compostos ativos, preservando
a sua atividade fungicida. Através de uma abordagem de desreplicação, foi possível,
numa subfração, identificar dois compostos – mirabilin B e penaresidin B –, cuja
atividade antifúngica já tinha sido documentada.
Este resultado reforça este tipo de abordagem como uma estratégia valiosa para priorizar
a análise das frações com atividade. No geral, este estudo destaca os organismos marinhos
como recursos promissores para a descoberta de novos e mais eficazes fármacos
antifúngicos.
Invasive fungal infections represent a global health threat. They are associated with high mortality and morbidity rates, in part due to the ineffectiveness of available antifungal agents. The rampant increase in infections recalcitrant to current antifungals has worsened this scenario and made the development of new and more effective antifungals a priority. The still unexplored marine biodiversity provides an unlimited source of new metabolites with potential clinical applications and may accelerate drug discovery. The weak investment in new antifungal drugs over last years, together with the emergence species resistant to current antifungal drugs, are widely acknowledged to contribute to the burden that these diseases cause in patients and healthcare systems. In this work, two libraries of 65 and 44 extracts from marine organisms of the Yucatan Peninsula, Mexico, were tested for antifungal activity against Candida species, opportunistic yeasts known to cause nosocomial invasive fungal infections. We have identified four marine extracts with high antifungal potential. All of them are fungicidal and, at least two, are minimally toxic to mammalian cells. The fractionation of promising extracts through bioguided assays coupled with biochemical and biophysical methodologies allowed partial purification of the active compounds while preserving their fungicidal activity. Through a dereplication approach, it was possible to identify two compounds - mirabilin B and penaresidin B - in one of the subfractions, which have already been reported to have antifungal activity. This finding underscores this type of approach as a valuable strategy for prioritizing the analysis of subsequent fractions. Overall, this study highlights marine organisms as promising resources for the discovery of new and more effective antifungal drugs.
Invasive fungal infections represent a global health threat. They are associated with high mortality and morbidity rates, in part due to the ineffectiveness of available antifungal agents. The rampant increase in infections recalcitrant to current antifungals has worsened this scenario and made the development of new and more effective antifungals a priority. The still unexplored marine biodiversity provides an unlimited source of new metabolites with potential clinical applications and may accelerate drug discovery. The weak investment in new antifungal drugs over last years, together with the emergence species resistant to current antifungal drugs, are widely acknowledged to contribute to the burden that these diseases cause in patients and healthcare systems. In this work, two libraries of 65 and 44 extracts from marine organisms of the Yucatan Peninsula, Mexico, were tested for antifungal activity against Candida species, opportunistic yeasts known to cause nosocomial invasive fungal infections. We have identified four marine extracts with high antifungal potential. All of them are fungicidal and, at least two, are minimally toxic to mammalian cells. The fractionation of promising extracts through bioguided assays coupled with biochemical and biophysical methodologies allowed partial purification of the active compounds while preserving their fungicidal activity. Through a dereplication approach, it was possible to identify two compounds - mirabilin B and penaresidin B - in one of the subfractions, which have already been reported to have antifungal activity. This finding underscores this type of approach as a valuable strategy for prioritizing the analysis of subsequent fractions. Overall, this study highlights marine organisms as promising resources for the discovery of new and more effective antifungal drugs.
Descrição
Palavras-chave
Microbiologia médica Infeções fúngicas invasivas Antifúngicos Biodiversidade marinha Produtos naturais Candida SPP