N-alkylimidazole derivatives as potential inhibitors of quorum sensing in Pseudomonas aeruginosa
Caleb Nketia Mensah,
Gilbert Boadu Ampomah,
Jehoshaphat Oppong Mensah,
Edward Ntim Gasu,
Caleb Impraim Aboagye,
Edmund Ekuadzi,
Nathaniel Owusu Boadi,
Lawrence Sheringham Borquaye
Affiliations
Caleb Nketia Mensah
Department of Chemistry, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
Gilbert Boadu Ampomah
Department of Chemistry, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
Jehoshaphat Oppong Mensah
Department of Chemistry, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
Edward Ntim Gasu
Department of Chemistry, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana; Central Laboratory, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
Caleb Impraim Aboagye
Department of Chemistry, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
Edmund Ekuadzi
Central Laboratory, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana; Department of Pharmacognosy, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
Nathaniel Owusu Boadi
Department of Chemistry, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
Lawrence Sheringham Borquaye
Department of Chemistry, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana; Central Laboratory, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana; Corresponding author.
Antimicrobial resistance is a threat to global public health. Microbial resistance is mediated by biofilm formation and virulence behavior during infection. Quorum sensing (QS), a cell-to-cell communication is frequently used by microbes to evade host immune systems. Inhibiting QS channels is a potential route to halt microbial activities and eliminate them. Imidazole has been shown to be a potent warhead in various antimicrobial agents. This study aims to evaluate alkyl-imidazole derivatives as potential inhibitors of QS and to explore the interactions of the compounds with LasR, a key protein in the QS machinery of Pseudomonas aeruginosa. The study revealed that imidazole derivatives with longer alkyl chains possessed better antimicrobial activities. Octylimidazole and decylimidazole emerged as compounds with better anti-virulence and biofilm inhibition properties while hexylimidazole showed the best inhibitory activity against Pseudomonas aeruginosa PAO1. The binding affinity of the compounds with LasR followed a similar trend as that observed in the QS inhibitory assays, suggesting that interaction with LasR may be important for QS inhibition.
