In order to expand the structure-activity relationship of tetramic acid molecules with structural similarity to the antibiotic reutericyclin, 22 compounds were synthesized and tested against a panel of clinically relevant bacteria. Key structural changes on the tetramic acid core affected antibacterial activity. Various compounds in the N-alkyl 3-acetyltetramic acid series exhibited good activity against Gram-positive bacterial pathogens including Bacillus anthracis, Propionibacterium acnes, Enterococcus faecalis, and both Methicillin-sensitive and -resistant Staphylococcus aureus.
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Antibacterial barbituric acid analogues inspired from natural 3-acyltetramic acids; synthesis, tautomerism and structure and physicochemical property-antibacterial activity relationships.
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Chemistry Research Laboratory, Mansfield Rd, University of Oxford, OX1 3TA, UK.
The synthesis, tautomerism and antibacterial activity of novel barbiturates is reported. In particular, 3-acyl and 3-carboxamidobarbiturates exhibited antibacterial activity, against susceptible and some resistant Gram-positive strains of particular interest is that these systems possess amenable molecular weight, rotatable bonds and number of proton-donors/acceptors for drug design as well as less lipophilic character, with physicochemical properties and ionic states that are similar to current antibiotic agents for oral and injectable use. Unfortunately, the reduction of plasma protein affinity by the barbituric core is not sufficient to achieve activity in vivo.
View Article and Find Full Text PDFDFT study of the Lewis acid mediated synthesis of 3-acyltetramic acids.
J Mol Model
May 2014
Institute of Applied Synthetic Chemistry, Vienna University of Technology, 1060, Vienna, Austria,
The synthesis of 3-acyltetramic acids by C-acylation of pyrrolidine-2,4-diones was studied by density functional theory (DFT). DFT was applied to the mycotoxin tenuazonic acid (TeA), an important representative of these bioactive natural compounds. Lewis acid mediated C-acylation in combination with previous pH-neutral domino N-acylation-Wittig cyclization can be used for the efficient preparation of 3-acyltetramic acids.
View Article and Find Full Text PDFStructure and tautomerism of tenuazonic acid--a synergetic computational and spectroscopic approach.
J Hazard Mater
April 2013
Vienna University of Technology, Institute of Applied Synthetic Chemistry, Getreidemarkt 9/163-OC, 1060 Vienna, Austria.
All reasonable tautomers and rotamers of tenuazonic acid, which is considered to be of the highest toxicity amongst the Alternaria mycotoxins, were investigated by DFT calculations at different levels of theory in gas phase and in solution to obtain optimized geometries for further examinations. Calculated NMR spectra of tautomeric structures are being presented and compared to experimental data to finally achieve a synergetic computational and spectroscopic approach for structure elucidation of 3-acetyltetramic acids, affording the predominant tautomer of tenuazonic acid in aqueous solution. Furthermore we were able to simulate the less hindered rotation of the exocyclic acetyl group, which occurs after dissociation of tenuazonic acid in protic solvents.
View Article and Find Full Text PDFN-substituted 3-acetyltetramic acid derivatives as antibacterial agents.
J Med Chem
March 2008
Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA.
In order to expand the structure-activity relationship of tetramic acid molecules with structural similarity to the antibiotic reutericyclin, 22 compounds were synthesized and tested against a panel of clinically relevant bacteria. Key structural changes on the tetramic acid core affected antibacterial activity. Various compounds in the N-alkyl 3-acetyltetramic acid series exhibited good activity against Gram-positive bacterial pathogens including Bacillus anthracis, Propionibacterium acnes, Enterococcus faecalis, and both Methicillin-sensitive and -resistant Staphylococcus aureus.
View Article and Find Full Text PDFA semiempirical SCF-MO study of the tautomeric forms of 3-acetyl tetronic- and tetramic acids.
J Comput Aided Mol Des
June 1990
Department of Chemistry, Imperial College, London, U.K.
A number of tautomeric geometries of 3-acetyl tetramic acid and 3-acetyl tetronic acid were examined using the AM1 and PM3 methods. The results are compared with experimental data and with studies using MNDO and older methods, with the conclusion that both AM1 and PM3 provide satisfactory models of the behaviour of these species.
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