RESUMO
A new worldwide concern has emerged with the recent emergence of infections caused by Candida auris. This reflects its comparative ease of transmission, substantial mortality, and the increasing level of resistance seen in the three major classes of antifungal drugs. Efforts to create a better design for structure-based drugs that described numerous modifications and the search for secondary metabolic structures derived from plant species are likely to reduce the virulence of several fungal pathogens. In this context, the present work aimed to evaluate in silico two naphthoquinones isolated from the roots of Capraria biflora, biflorin, and its dimmer, bis-biflorin, as potential inhibitors of Candida auris polymerase. Based on the simulation performed with the two naphthoquinones, biflorin and bis-biflorin, it can be stated that bis-biflorin showed the best interactions with Candida auris polymerase. Still, biflorin also demonstrated favorable coupling energy. Predictive pharmacokinetic assays suggest that biflorin has high oral bioavailability and more excellent metabolic stability compared to the bis-biflorin analogue. constituting a promising pharmacological tool.Communicated by Ramaswamy H. Sarma.
Assuntos
Candida auris , Naftoquinonas , Simulação de Acoplamento Molecular , Naftoquinonas/farmacologia , Naftoquinonas/química , Antifúngicos/farmacologia , Testes de Sensibilidade MicrobianaRESUMO
Dengue (DENV), Zica virus (ZIKV), and Chikungunya fever (CHIK) are tropical diseases that have caused a lot of problems in general worldwide. Transmitted by mosquitoes of the species Aedes aegypti and albopictus, they have not been completely eradicated in the country, and their proliferation has only increased in the Northeast region. Within the structure of the virus, it is possible to verify the presence of glycoprotein SN1, which is responsible for its replication. If this macromolecule is inhibited using a specific or complex linker, it can interrupt its replication activity. An alternative to this problem has been using structures derived from natural products that have pharmacological properties. A dynamic and molecular docking combined study used computational simulation in the four isomeric forms of bixin against the SN1 protein. The Z,E-bixin and E,E-bixin isomers, both with affinity energy -6.7 and -6.5 Kcal/mol, presented the best results. Thus, bixin and its isomers, found in annatto seeds, maybe an initial proposal in the search for prototype compounds to study to fight this lethal virus in the future.Communicated by Ramaswamy H. Sarma.