Design,synthesis, in-silico studies and biological screening of quinazolinone analogues as potential antibacterial agents against MRSA |
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| Institution: | 1. Medicinal Plants Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran;2. Persian Medicine and Pharmacy Research Center, Tehran University of Medical Sciences, Tehran, Iran;3. Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran;4. Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran;5. Social Determinants of Health Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran;6. Department of Pharmaceutical Biotechnology, Faculty of Pharmacy and Biotechnology Research Center, Tehran University of Medical Sciences, Tehran, Iran;7. Diabetes Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran;8. Department of Biotechnology, Iranian Research Organization for Science and Technology, P.O. Box 3353-5111, Tehran, Iran;9. Food and Drug Research Institute, Food and Drug Administration, MOHE, Tehran, Iran;10. Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran;1. Department of Studies in Chemistry, University of Mysore, Manasagangotri, Mysore 570 006, Karnataka, India;2. Department of Chemistry, KLE Society''s Jagadguru Tontadarya College, Gadag-582101, Karnataka, India;1. Key Laboratory of Small Fuctional Organic Molecule, Ministry of Education and College of Life Science, Jiangxi Normal University, Nanchang, Jiangxi 330022, China;2. Key Laboratory of Green Chemistry, Jiangxi Province, Nanchang, Jiangxi 330022, China |
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| Abstract: | Type or The emergence of resistance to antibiotic has developed a complicated situation in the treatment of bacterial infections. Considering the antimicrobial resistance phenomenon as one of the greatest challenge of medicinal chemists for search of better anti-bacterial agents, which have potential narrow spectrum activity with low development of resistance potential and low toxicity to host. Cross-linking of peptidoglycan is a key step catalyze by Penicillin binding protein (PBP) to maintain integrity of cell wall in bacterial cell. However, these Penicillin binding protein (PBP) has developed resistance in methicillin-resistant Staphylococcus aureus (MRSA) due to acquisition of additional PBP2a. Various Quinazolinone analogues are reported in literature as potential anti-bacterial agents against MRSA. In present study new quinazolinone analogues has been designed, guided by molecular docking, In-silico and MM-GBSA study. Newly designed molecules have been synthesized by medicinal chemistry route and their characterization was done by using IR, NMR, & HR-MS techniques. Biological evaluation of synthesized compounds has been done on wild type Gram-negative (Escherichia coli), Gram-positive (Staphylococcus aureus) and resistant MRSA bacterial strains using Streptomycin, Kanamycin and Linezolid as standard drugs respectively. The in vitro evaluation results have shown that compound 5f is active with MIC value 15.625 μg/mL against S. aureus and with MIC value 31.25 μg/mL against MRSA. |
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| Keywords: | Penicillin binding protein 2a Antibacterial Microbial resistance Docking MM-GBSA |
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