Estudio in silico dirigido al descubrimiento de inhibidores de la enzima FlaA1 de la Helicobacter pylori

Abstract

H. pylori is a gram negative bacterium, it is found in two thirds of the world population and it is related to the majority of gastric diseases, therefore its eradication constitutes a public health problem. One of the enzymes related to this bacterium that has been found to be a promising molecular target is FlaA1. It is the first enzyme involved in the pseudaminic acid pathway, a unique sugar in microorganisms, responsible for the glycosylation of flagellin that is important for flagellar assembly in Helicobacter pylori. In addition, it is related to the synthesis of lipopolysaccharides, which facilitate the adhesion and subsequent colonization of the bacteria in the gastric epithelium. To date, six inhibitors against FlaA1 have been reported. However, these have not been as effective when applied in cell tests, so the discovery of more efficient compounds is required with respect to those already reported. For this, an alternative is natural products, since they present molecular scaffolds and pharmacophore patterns that are biologically relevant and therefore are widely used in drug discovery. Therefore, in this thesis work, a computational study was developed in which several compounds from natural products were identified as possible inhibitors of the enzyme. These molecules presented in common, a phenyl ring with substitutions for-OH and / or meta-OH that are also found in the compounds reported as inhibitors. In addition, several of these compounds had interactions with the active site residues of the enzyme, so it is expected that they also have experimental activity.