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In silico study and biological screening of benzoquinazolines as potential antimicrobial agents against methicillin-resistant Staphylococcus aureus, carbapenem-resistant Klebsiella pneumoniae, and fluconazole-resistant Candida albicans.

Authors
  • Abuelizz, Hatem A1
  • Marzouk, Mohamed2
  • Bakhiet, Ahmed1
  • Abdel-Aziz, Marwa M3
  • Ezzeldin, Essam1
  • Rashid, Harunor4
  • Al-Salahi, Rashad5
  • 1 Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, PO Box 2457, Riyadh, 11451, Saudi Arabia. , (Saudi Arabia)
  • 2 Chemistry of Tanning Materials and Leather Technology Department, Organic Chemical Industries Division, National Research Centre, 33 El-Bohouth St. Former El-Tahrir St., Dokki, Cairo, 12622, Egypt. , (Egypt)
  • 3 Medical Microbiology at the Regional Center for Mycology and Biotechnology, Al-Azhar University, Cairo, Egypt. , (Egypt)
  • 4 National Centre for Immunisation Research and Surveillance (NCIRS), Kids Research at The Children's Hospital, Faculty of Medicine and Health, The University of Sydney, Westmead, NSW, 2145, Australia. , (Australia)
  • 5 Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, PO Box 2457, Riyadh, 11451, Saudi Arabia. Electronic address: [email protected] , (Saudi Arabia)
Type
Published Article
Journal
Microbial Pathogenesis
Publisher
Elsevier
Publication Date
Aug 25, 2021
Volume
160
Pages
105157–105157
Identifiers
DOI: 10.1016/j.micpath.2021.105157
PMID: 34454024
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Globally, antibiotic-resistant pathogens have become a serious threat to public health. The use of drugs having structures different from those applied in the clinical treatments of bacterial infections is a well-known potential solution to the antibiotic resistance crisis. Benzo-[g]-quinazolines were identified by our research group as a new class of antimicrobial agents. Herein, to follow-up the research on such compounds, three benzo-[g]-quinazolines (1-3) were studied, as in vitro antibacterial candidates against methicillin-resistant Staphylococcus aureus (MRSA), carbapenem-resistant Klebsiella pneumoniae, and fluconazole-resistant Candida albicans, as well. The minimum inhibitory concentration (MIC) assay for benzoquinazolines was carried out via the calorimetric broth microdilution method using the XTT assay in comparison with vancomycin, ciprofloxacin, and ketoconazole as reference drugs. The target compounds 1-3 revealed high variation in their activity against the examined resistant microbial strains. Benzoquinazoline 3 exhibited a more potent effect against the resistant strains compared with the reference drugs. A docking study was performed to identify the interactions between the benzoquinazolines 1-3 and ligand proteins (OXA-48 carbapenemase, β-lactamase, and sterol 14-alpha demethylase (CYP51)) at the active sites. Benzoquinazolines 1-3 showed very weak cytotoxicity against human lung fibroblast normal cells (WI-38). The targets showed promising antimicrobial effects against the three resistant strains. These findings may inform future inhibitor discoveries targeting penicillin-binding proteins. Copyright © 2021 Elsevier Ltd. All rights reserved.

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