Τίτλος:
Synthesis, biological evaluation and structure-activity relationships of 5-arylidene tetramic acids with antibacterial activity against methicillin-resistant Staphylococcus aureus
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
The steady rise of the antimicrobial resistance is a major global threat to human health that requires the urgent need for novel antibiotics. In this work we report the synthesis of a small library of 3-subsituted-5-arylidene tetramic acids in order to investigate the scope of our previously established methodology via an intermediate oxazolone and their antimicrobial activity. From this series of 14 tetramic acids, 11 derivatives are novel and one of them is a Schiff base, which was structurally characterized with single-crystal X-ray analysis and NMR spectroscopy. The compounds incorporating a lipophilic acyl group at carbon-3 of the ring showed moderate to high activity with minimum inhibitory activity of 4–32 μg/mL against methicillin-resistant Staphylococcus aureus (MRSA), accompanied by no human cell toxicity and hemolytic activity within the tested concentration range. The substituent at para position of the aryl ring seemed to have no or little effect on the antimicrobial activity of these compounds. © 2020 Elsevier Ltd
Συγγραφείς:
Matiadis, D.
Tsironis, D.
Stefanou, V.
Boussias, S.
Panagiotopoulou, A.
McKee, V.
Igglessi-Markopoulou, O.
Markopoulos, J.
Περιοδικό:
Bioorganic and Medicinal Chemistry Letters
Εκδότης:
Elsevier Ireland Ltd
Λέξεις-κλειδιά:
5 arylidene tetramic acid derivative; antiinfective agent; n acetyl 3 acetyl 5 (4 chlorobenzylidene)tetramic acid; n acetyl 3 acetyl 5 (4 fluorobenzylidene)tetramic acid; n acetyl 3 acetyl 5 (4 methoxybenzylidene)tetramic acid; n acetyl 3 acetyl 5 (4 methylbenzylidene)tetramic acid; n acetyl 3 acetyl 5 (4 nitrobenzylidene)tetramic acid; n acetyl 3 acetyl 5 (4 trifluoromethylbenzylidene)tetramic acid; n acetyl 3 butyryl 5 (4 methoxybenzylidene)tetramic acid; n acetyl 5 benzylidene 3 decanoyltetramic acid; n acetyl 5 benzylidene 3 octanoyltetramic acid; n acetyl 5 benzylidene 3 tetradecanoyltetramic acid; Schiff base; tetramic acid derivative; unclassified drug; 2 pyrrolidone derivative; antiinfective agent; tetramic acid, antibacterial activity; Article; controlled study; cytotoxicity; drug synthesis; hemolysis; hydrogen bond; methicillin resistant Staphylococcus aureus; minimum inhibitory concentration; nonhuman; nuclear magnetic resonance spectroscopy; Staphylococcus aureus; structure activity relation; X ray crystallography; Candida albicans; chemistry; conformation; drug effect; Escherichia coli; methicillin resistant Staphylococcus aureus; microbial sensitivity test; structure activity relation; synthesis, Anti-Bacterial Agents; Candida albicans; Crystallography, X-Ray; Escherichia coli; Magnetic Resonance Spectroscopy; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Molecular Conformation; Pyrrolidinones; Staphylococcus aureus; Structure-Activity Relationship
DOI:
10.1016/j.bmcl.2020.127107
