Synthesis, Structure Elucidation and Biological Activities of Some Novel 4(3H)-Quinazolinones as Anti-Biofilm Agents

Author(s): Sevda Türk, Sevgi Karakuş*, Abdulilah Ece, Seyhan Ulusoy, Gülgün Bosgelmez-Tınaz.

Journal Name: Letters in Drug Design & Discovery

Volume 16 , Issue 3 , 2019

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Graphical Abstract:


Background: Pseudomonas aeruginosa is an opportunistic pathogen that causes chronic infections in immunocompromised patients. The inhibition of Quorum Sensing (QS) system has been recognized as an attractive strategy for the treatment of P. aeruginosa infections. In the present study, a series of novel 2-methyl-3-[4-(substituedaminosulfonyl)phenyl]-4(3H)-quinazolinones (1-8) were synthesized and tested for their biofilm formation and swarming motility inhibitory activities in P. aeruginosa PA01.

Findings: These compounds were found to reduce biofilm formation by 20-32% and swarming motility by 51-62% in P. aeruginosa PA01 at a concentration of 12.5µM. Molecular docking studies were also performed to elucidate the possible key interactions of these compounds with the active site of the P. aeruginosa QS receptor LasR. Furthermore, some molecular properties related to drug likeness and ADME were predicted.

Results and Conclusion: Results of this study demonstrated that compounds 1-8 can influence QS-regulated biofilm formation and swarming motility in P. aeruginosa PA01 by binding LasR protein and could be developed as anti-biofilm agents to treat chronic biofilm associated infections caused by P. aeruginosa and other clinically significant pathogens.

Keywords: 4(3H)-Quinazolinones, structure elucidation, LasR protein, Pseudomonas aeruginosa, quorum sensing, biofilm formation.

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Article Details

Year: 2019
Page: [313 - 321]
Pages: 9
DOI: 10.2174/1570180815666180621101123
Price: $58

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