Evaluation of the Antibacterial and Investigation of the Molecular Docking of New Derivatives of ۱, ۳, ۴-Oxadiazole as Inhibitors of Quorum Sensing System in the Human Pathogen Pseudomonas Aeruginosa

Background: Oxadiazoles are a group of anti-inflammatory compounds that have a wide range of activitydue to their higher efficacy. Pseudomonas aeruginosa is an opportunistic pathogen and a major pathogen ofnosocomial infections. This study aimed to evaluate the antibacterial and investigation of the molecular dockingof new derivatives of ۱, ۳, ۴-oxadiazole against P. aeruginosa, in vitro & in silico.Materials and Methods: Four new derivatives were synthesized and added to our previous synthetic derivativesof ۱, ۳, ۴-oxadiazole. The antibacterial activity of all derivatives was measured based on three standard species ofP. aeruginosa using inhibition zone (IZ) and minimum inhibitory concentration (MIC) and minimum bactericidalconcentration (MBC) methods. Then, employing the computational design of the drug by the molecular dockingmethod, the inhibitory effect of synthetic compounds on the LasR regulatory protein of P. aeruginosa quorumsensing system was investigated, which plays an important role in regulating the expression of pathogenic genesin bacteria.Results: The chemical structures of new compounds were characterized by IR spectra and ۱H-NMR. A varietyof inhibitory effects were observed by the synthesized compounds – compound ۴d and ۴g, in particular. Also,the inhibitory effect of these two compounds on the LasR regulatory protein under the control of the quorumsensing system in P. aeruginosa was demonstrated by molecular docking.Conclusions: The results of this study showed that the two compounds containing the functional group ofnaphthalene and fluorophenyl have a significant effect on the inhibition of P. aeruginosa, as well as on the LasRprotein of this bacterium.

کلیدواژه ها:

Oxadiazoles ، Antibacterial ، Molecular docking ، Fluorophenyl ، Naphthalene