VII Simposio Internacional de Química 2019 "SIQ 2019" -VII Conferencia "Ciencias Químicas"

VII Simposio Internacional de Química 2019

SIQ 2019

VII Conferencia "Ciencias Químicas"

Multicomponent preparation, characterization and in silico analysis of potential inhibitors of Pseudomonas aeruginosa quorum sensing receptor LasR

Resumen [ES]

Pseudomonas aeruginosa is a pathogenic Gram-negative bacterium responsible for several serious infections, being the main cause of pulmonary infections in patients with cystic fibrosis. The expression of the virulence and toxicity factors in the parasite is carried out by a mechanism known as quorum sensing, controlled by various transcription factors, among which is the protein LasR. Blocking this process contributes to prevent damages in animals from the pathogen. Therefore, the synthesis of molecules that can inhibit key proteins of quorum sensing represents an advantage in the therapy against P. aeruginosa, where the abuse of antibiotics has brought the emergence of resistant strains. Triphenyl-amide-type compounds that inhibit LasR have been reported and represent a scaffold on which to develop novel bioactive structures. In our laboratory, we designed several furanic diamides with potential inhibitory activity against LasR. The analogs were synthesized by the Ugi four-component reaction and their identities were verified by spectroscopic techniques (1H, 13C, DEPT-135 NMR and HH-COZY, HMBC, me-HSQC, NOESY). Additionally, we carried out a molecular docking study of the synthesized ligands against LasR. Our results indicate that the synthesized compounds have similar interactions to that of reported inhibitors, which suggests the possibility that our compounds may be inhibitors of LasR. This work constitutes the first report, as far as we know, of a multicomponent approach for the synthesis of potential LasR inhibitors, employing the Ugi multicomponent reaction. The compounds were obtained in a single step with high purity, without requiring further purification in most instances.

Resumen [EN]

Pseudomonas aeruginosa is a pathogenic Gram-negative bacterium responsible for several serious infections, being the main cause of pulmonary infections in patients with cystic fibrosis. The expression of the virulence and toxicity factors in the parasite is carried out by a mechanism known as quorum sensing, controlled by various transcription factors, among which is the protein LasR. Blocking this process contributes to prevent damages in animals from the pathogen. Therefore, the synthesis of molecules that can inhibit key proteins of quorum sensing represents an advantage in the therapy against P. aeruginosa, where the abuse of antibiotics has brought the emergence of resistant strains. Triphenyl-amide-type compounds that inhibit LasR have been reported and represent a scaffold on which to develop novel bioactive structures. In our laboratory, we designed several furanic diamides with potential inhibitory activity against LasR. The analogs were synthesized by the Ugi four-component reaction and their identities were verified by spectroscopic techniques (1H, 13C, DEPT-135 NMR and HH-COZY, HMBC, me-HSQC, NOESY). Additionally, we carried out a molecular docking study of the synthesized ligands against LasR. Our results indicate that the synthesized compounds have similar interactions to that of reported inhibitors, which suggests the possibility that our compounds may be inhibitors of LasR. This work constitutes the first report, as far as we know, of a multicomponent approach for the synthesis of potential LasR inhibitors, employing the Ugi multicomponent reaction. The compounds were obtained in a single step with high purity, without requiring further purification in most instances.

Sobre el ponente

Marcos Rafael Conde González

Mr. Marcos Rafael Conde González

UH Flag of Cuba
Información Práctica
English (US)
No definido
30 minutos
No definido
Autores
Francisco Coll Manchado
Yamilet Coll Garcia
Elena Moreno Castillo
Mr. Marcos Rafael Conde González
Giselle Hernández Campoalegre
Juan Pablo Figueroa Macias
Palabras clave
molecular docking
multicomponent reactions
pseudomonas aeruginosa
quorum sensing