U.S. flag

An official website of the United States government


Main content area

Molecular docking and biological evaluation of novel urea-tailed mannich base against Pseudomonas aeruginosa

Mohanvel, Sucharitha Kannappan, Ravichandran, Vinothkannan, Kamalanathan, Chakkaravarthi, Satish, Ann Susan, Ramesh, Samiraj, Lee, Jintae, Rajasekharan, Satish Kumar
Microbial pathogenesis 2019 v.130 pp. 104-111
Pseudomonas aeruginosa, active sites, antimicrobial properties, biofilm, computer simulation, dose response, genes, mechanism of action, messenger RNA, moieties, multiple drug resistance, pathogenesis, pathogens, pyocyanin, quorum sensing, urea
Emergence of multi-drug resistant bacterial pathogens is escalating and it is essential to develop novel strategies to combat these super bugs. LasR is a regulator switch that plays a vital role in quorum sensing (QS) and pathogenesis of Pseudomonas aeruginosa. The present study reports two novel Mannich base (1-(phenyl (o-tolylamino) methyl) urea and 3-((1H-Imidazole-1-yl) methylnaphthalene-2-ol with enhanced anti-QS and antibiofilm activities. Synthetic compound revealed prolific interaction patterns with LasR quorum sensing receptor and showed to exhibit LasR antagonistic activities in P. aeruginosa. In-vitro LasR-inhibitory activities were further confirmed by biofilm and pyocyanin inhibition assays which showed a dose-dependent activity. The Mannich base also repressed the mRNA transcripts levels of lasA and lasB genes, confirming its active role in LasR inhibitory activity. Importantly, C1 and C2 played a crucial role in antagonizing LasR receptor by forming H-bonds with Tyr47 in the LasR active site and the presence of urea moiety on one of the Mannich base was a discrete advantage. Taken together, the insilico and invitro assays revealed similar evidences, thus confirming the mode of action of the Mannich bases. Overall the findings will assist in drug designing and for developing newer drugs with Mannich bases and its derivatives for treatment of P. aeruginosa.