Searching hit potential antimicrobials in natural compounds space against biofilm formation
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Fecha
2020
Autores
Pestana-Nobles, Roberto
Leyva-Rojas, Jorge A.
Yosa, Juvenal
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Editor
MDPI
Resumen
Biofilms are communities of microorganisms that can colonize biotic and abiotic surfaces
and thus play a significant role in the persistence of bacterial infection and resistance to antimicrobial.
About 65% and 80% of microbial and chronic infections are associated with biofilm formation,
respectively. The increase in infections by multi-resistant bacteria instigates the need for the
discovery of novel natural-based drugs that act as inhibitory molecules. The inhibition of diguanylate
cyclases (DGCs), the enzyme implicated in the synthesis of the second messenger, cyclic diguanylate
(c-di-GMP), involved in the biofilm formation, represents a potential approach for preventing the
biofilm development. It has been extensively studied using PleD protein as a model of DGC for in
silico studies as virtual screening and as a model for in vitro studies in biofilms formation. This study
aimed to search for natural products capable of inhibiting the Caulobacter crescentus enzyme PleD.
For this purpose, 224,205 molecules from the natural products ZINC15 database, have been evaluated
through molecular docking and molecular dynamic simulation. Our results suggest trans-Aconitic
acid (TAA) as a possible starting point for hit-to-lead methodologies to obtain new inhibitors of the
PleD protein and hence blocking the biofilm formation.
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Palabras clave
Biofilms, Virtual screening, Molecular dynamics, Natural products, Binding energy, Trans-aconitic acid, hit-to-lead