Synthesis, Characterization, Antibacterial Activity, and Computer-Aided Design of Novel Quinazolin-2, 4-dione Derivatives as Potential Inhibitors Against Vibrio cholerae. (January 2020)

• Record Type: Journal Article
• Authors: El-Naggar, Mohamed; Mohamed, Mahmoud Eldeeb; Mosallam, Ahmed Mohamed; Salem, Wesam; Rashdan, Huda RM; Abdelmonsef, Aboubakr Haredi
• Is Part Of: Evolutionary bioinformatics online. Volume 16(2020)
• Publication Date: 2020-01
• Subjects: Vibrio cholerae -- OmpU -- quinazolin-2, 4-dione -- Gram-negative bacteria -- in silico docking; Bioinformatics -- Periodicals; Evolutionary computation -- Periodicals; Genetic programming (Computer science) -- Periodicals; Computational Biology; Evolution, Molecular; Bioinformatics; Electronic journals; Periodicals; Fulltext; Internet Resources; Periodicals; Periodicals; 576.8
• DOI: 10.1177/1176934319897596
• Languages: English
• ISSNs: 1176-9343

Abstract

Cholera is a bacterial disease featured by dehydration and severe diarrhea. It is mainly caused by alimentary infection with Vibrio cholerae . Due to the wide applicability of quinazolin-2, 4-dione compounds in medicinal and pharmaceutical chemistry, a new series of N -containing heterocyclic compounds was synthesized. We used the in silico docking method to test the efficacy of quinazolin-2, 4-dione compounds in the prevention of cholera in humans. The newly synthesized compounds showed strong interactions and good binding affinity to outer membrane protein OmpU. Moreover, the pharmacokinetic properties of the newly synthesized compounds, such as absorption, distribution, metabolic, excretion, and toxicity (ADMET), were predicted through in silico methods. Compounds with acceptable pharmacokinetic properties were tested as novel ligand molecules. The synthesized compounds were evaluated in vitro for their antibacterial activity properties against Gram-negative Escherichia coli O78 strain using the minimum inhibition concentration (MIC) method. Compounds2 and6 showed reproducible, effective antibacterial activity. Hence, our study concludes that the quinazolin-2, 4-dione derivatives1 to8 may be used as promising drug candidates with potential value for the treatment of cholera disease.