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Tytuł:
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Antibacterial, antibiofilm and molecular modeling study of some antitumor thiazole based chalcones as a new class of DHFR inhibitors.
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Autorzy:
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Alrohily WD; College of Pharmacy, Taibah University, P.O. Box 30039, Al-Madinah Al-Munawarah, 41477, Saudi Arabia.
Habib ME; Faculty of Pharmacy, Horus University, New Damietta, 34517, Egypt.
El-Messery SM; Department of Pharmacognosy and Pharmaceutical Chemistry, College of Pharmacy, Taibah University, P.O. Box 30039, Al-Madinah, Al-Munawarah, 41477, Saudi Arabia; Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura, 35516, Egypt.
Alqurshi A; Department of Pharmaceutics and Pharmaceutical Technology, College of Pharmacy, Taibah University, P.O. Box 30039, Al-Madinah, Al-Munawarah, 41477, Saudi Arabia.
El-Subbagh H; Department of Medicinal Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura, 35516, Egypt.
Habib EE; Department of Pharmaceutics and Pharmaceutical Technology, College of Pharmacy, Taibah University, P.O. Box 30039, Al-Madinah, Al-Munawarah, 41477, Saudi Arabia; Department of Microbiology, Faculty of Pharmacy, Mansoura University, Mansoura, 35516, Egypt. Electronic address: .
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Źródło:
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Microbial pathogenesis [Microb Pathog] 2019 Nov; Vol. 136, pp. 103674. Date of Electronic Publication: 2019 Aug 22.
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Typ publikacji:
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Journal Article
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Język:
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English
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Imprint Name(s):
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Original Publication: London ; Orlando : Academic Press, c1986-
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MeSH Terms:
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Anti-Bacterial Agents/*pharmacology
Biofilms/*drug effects
Chalcones/*pharmacology
Folic Acid Antagonists/*pharmacology
Gram-Negative Bacteria/*drug effects
Gram-Positive Bacteria/*drug effects
Biofilms/growth & development ; Gram-Negative Bacteria/growth & development ; Gram-Positive Bacteria/growth & development ; Microbial Sensitivity Tests ; Molecular Docking Simulation ; Protein Binding ; Tetrahydrofolate Dehydrogenase/chemistry ; Tetrahydrofolate Dehydrogenase/metabolism
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Contributed Indexing:
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Keywords: Antibacterial & antitumor activity; DHFR inhibitors; Molecular modeling; Thiazole based chalcones
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Substance Nomenclature:
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0 (Anti-Bacterial Agents)
0 (Chalcones)
0 (Folic Acid Antagonists)
EC 1.5.1.3 (Tetrahydrofolate Dehydrogenase)
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Entry Date(s):
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Date Created: 20190826 Date Completed: 20200310 Latest Revision: 20200310
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Update Code:
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20240105
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DOI:
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10.1016/j.micpath.2019.103674
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PMID:
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31446042
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Some synthesized antitumor derivatives of thiazole based chalcones including thiazolo[2,3-b]quinazoline and pyrido[4,3-d]thiazolo[3,2-a]pyrimidine analogues were subjected to be tested against standard microbial strains. Compound 18 showed higher activity against both Gram-positive and Gram-negative bacteria with MIC of 1.0, 1.0, 2.0, 2.0 and 4.0 μg/ml against S. aureus, B. subtilis, M. luteus, E. coli and P. aeuroginosa respectively which is better than ampicillin and very relative to ciprofloxacin standards. Moreover, this compound shows a good anti-biofilm activity against the Gram positive bacteria. Molecular docking studies of synthesized compounds against DHFR enzyme were carried out. Interestingly, active anticancer candidates 22,38, 40 and 41 in addition to most active antimicrobial agents 15, 18 and 20 bind to DHFR with nearly the same amino acid residues as MTX especially mentioning Arg28, Arg70, Asn64 and Lys68 which support our hypothesis that these compounds could act as antitumor or antibacterial via DHFR inhibition. Flexible alignment and surface mapping techniques have further provided lipophilic distributions supporting effective binding to DHFR. ADMET calculations for compounds 15, 18 and 20 suggested that they could be good orally absorbed antibacterial agents while compound 38 could be an orally absorbed anticancer agent with diminished toxicity. The results highlight studied thiazole based chalcones as efficient leads for designing new future antibacterial drug candidates.
(Copyright © 2019 Elsevier Ltd. All rights reserved.)
