Design and synthesis of new quinazolinone derivatives: investigation of antimicrobial and biofilm inhibition effects.

Autor: Hassan RM; Medicinal and Pharmaceutical Chemistry Department, Pharmaceutical and Drug Industries Research Institute, National Research Centre (ID: 60014618), P.O. 12622, Dokki, Giza, Egypt. rashahassan_pharma@yahoo.ca., Yehia H; Chemistry of Natural and Microbial Products Department, Pharmaceutical and Drug Industries Research Institute, National Research Centre (ID: 60014618), P.O. 12622, Dokki, Giza, Egypt., El-Behairy MF; Department of Organic and Medicinal Chemistry, Faculty of Pharmacy, University of Sadat City, 32897, Sadat City, Egypt., El-Azzouny AA; Medicinal and Pharmaceutical Chemistry Department, Pharmaceutical and Drug Industries Research Institute, National Research Centre (ID: 60014618), P.O. 12622, Dokki, Giza, Egypt., Aboul-Enein MN; Medicinal and Pharmaceutical Chemistry Department, Pharmaceutical and Drug Industries Research Institute, National Research Centre (ID: 60014618), P.O. 12622, Dokki, Giza, Egypt. mnaboulenein@yahoo.com.
Jazyk: angličtina
Zdroj: Molecular diversity [Mol Divers] 2024 Apr 24. Date of Electronic Publication: 2024 Apr 24.
DOI: 10.1007/s11030-024-10830-y
Abstrakt: New quinazolin-4-ones 9-32 were synthesized in an attempt to overcome the life-threatening antibiotic resistance phenomenon. The antimicrobial screening revealed that compounds 9, 15, 16, 18, 19, 20 and 29 are the most broad spectrum antimicrobial agents in this study with safe profile on human cell lines. Additionally, compounds 19 and 20 inhibited biofilm formation in Pseudomonas aeruginosa, which is regulated by quorum sensing system, at sub-minimum inhibitory concentrations (sub-MICs) with IC 50 values 3.55 and 6.86 µM, respectively. By assessing other pseudomonal virulence factors suppression, it was found that compound 20 decreased cell surface hydrophobicity compromising bacterial cells adhesion, while both compounds 19 and 20 curtailed the exopolysaccharide production which constitutes the major component of the matrix binding biofilm components together. Also, at sub-MICs Pseudomonas cells twitching motility was impeded by compounds 19 and 20, a trait which augments the cells pathogenicity and invasion potential. Molecular docking study was performed to further evaluate the binding mode of candidates 19 and 20 as inhibitors of P. aeruginosa quorum sensing transcriptional regulator PqsR. The achieved results demonstrate that both compounds bear promising potential for discovering new anti-biofilm and quorum quenching agents against Pseudomonas aeruginosa without triggering resistance mechanisms as the normal bacterial life cycle is not disturbed.
(© 2024. The Author(s).)
Databáze: MEDLINE
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