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In silico design and enantioselective synthesis of functionalized monocyclic 3-amino-1-carboxymethyl-β-lactams as inhibitors of penicillin-binding proteins of resistant bacteria

(2018) CHEMISTRY-A EUROPEAN JOURNAL. 24(57). p.15254-15266
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Abstract
As a complement to the renowned bicyclic beta-lactam antibiotics, monocyclic analogues provide a breath of fresh air in the battle against resistant bacteria. In that framework, the present study discloses the in silico design and unprecedented ten-step synthesis of eleven nocardicin-like enantiomerically pure 2-{3-[2-(2-aminothiazol-4-yl)-2-(methoxyimino)acetamido]-2-oxoazetidin-1-yl}acetic acids starting from serine as a readily accessible precursor. The capability of this novel class of monocyclic 3-amino-beta-lactams to inhibit penicillin-binding proteins (PBPs) of various (resistant) bacteria was assessed, revealing the potential of alpha-benzylidenecarboxylates as interesting leads in the pursuit of novel PBP inhibitors. No deactivation by representative enzymes belonging to the four beta-lactamase classes was observed, while weak inhibition of class C beta-lactamase P99 was demonstrated.
Keywords
antibiotics, biological activity, chiral pool, drug design, lactams, BETA-LACTAMASE INHIBITORS, ESCHERICHIA-COLI, BIOLOGICAL EVALUATION, CONVENIENT SYNTHESIS, LEAVING GROUP, D-ALANINE, ANTIBIOTICS, CEPHALOSPORINS, CHEMISTRY, ACIDS

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Citation

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MLA
Decuyper, Lena, et al. “In Silico Design and Enantioselective Synthesis of Functionalized Monocyclic 3-Amino-1-Carboxymethyl-β-Lactams as Inhibitors of Penicillin-Binding Proteins of Resistant Bacteria.” CHEMISTRY-A EUROPEAN JOURNAL, vol. 24, no. 57, 2018, pp. 15254–66.
APA
Decuyper, L., Deketelaere, S., Vanparys, L., Jukič, M., Sosič, I., Sauvage, E., … D’hooghe, M. (2018). In silico design and enantioselective synthesis of functionalized monocyclic 3-amino-1-carboxymethyl-β-lactams as inhibitors of penicillin-binding proteins of resistant bacteria. CHEMISTRY-A EUROPEAN JOURNAL, 24(57), 15254–15266.
Chicago author-date
Decuyper, Lena, Sari Deketelaere, Lore Vanparys, Marko Jukič, Izidor Sosič, Eric Sauvage, Ana Maria Amoroso, et al. 2018. “In Silico Design and Enantioselective Synthesis of Functionalized Monocyclic 3-Amino-1-Carboxymethyl-β-Lactams as Inhibitors of Penicillin-Binding Proteins of Resistant Bacteria.” CHEMISTRY-A EUROPEAN JOURNAL 24 (57): 15254–66.
Chicago author-date (all authors)
Decuyper, Lena, Sari Deketelaere, Lore Vanparys, Marko Jukič, Izidor Sosič, Eric Sauvage, Ana Maria Amoroso, Olivier Verlaine, Bernard Joris, Stanislav Gobec, and Matthias D’hooghe. 2018. “In Silico Design and Enantioselective Synthesis of Functionalized Monocyclic 3-Amino-1-Carboxymethyl-β-Lactams as Inhibitors of Penicillin-Binding Proteins of Resistant Bacteria.” CHEMISTRY-A EUROPEAN JOURNAL 24 (57): 15254–15266.
Vancouver
1.
Decuyper L, Deketelaere S, Vanparys L, Jukič M, Sosič I, Sauvage E, et al. In silico design and enantioselective synthesis of functionalized monocyclic 3-amino-1-carboxymethyl-β-lactams as inhibitors of penicillin-binding proteins of resistant bacteria. CHEMISTRY-A EUROPEAN JOURNAL. 2018;24(57):15254–66.
IEEE
[1]
L. Decuyper et al., “In silico design and enantioselective synthesis of functionalized monocyclic 3-amino-1-carboxymethyl-β-lactams as inhibitors of penicillin-binding proteins of resistant bacteria,” CHEMISTRY-A EUROPEAN JOURNAL, vol. 24, no. 57, pp. 15254–15266, 2018.
@article{8598660,
  abstract     = {As a complement to the renowned bicyclic beta-lactam antibiotics, monocyclic analogues provide a breath of fresh air in the battle against resistant bacteria. In that framework, the present study discloses the in silico design and unprecedented ten-step synthesis of eleven nocardicin-like enantiomerically pure 2-{3-[2-(2-aminothiazol-4-yl)-2-(methoxyimino)acetamido]-2-oxoazetidin-1-yl}acetic acids starting from serine as a readily accessible precursor. The capability of this novel class of monocyclic 3-amino-beta-lactams to inhibit penicillin-binding proteins (PBPs) of various (resistant) bacteria was assessed, revealing the potential of alpha-benzylidenecarboxylates as interesting leads in the pursuit of novel PBP inhibitors. No deactivation by representative enzymes belonging to the four beta-lactamase classes was observed, while weak inhibition of class C beta-lactamase P99 was demonstrated.},
  author       = {Decuyper, Lena and Deketelaere, Sari and Vanparys, Lore and Jukič, Marko and Sosič, Izidor and Sauvage, Eric and Amoroso, Ana Maria and Verlaine, Olivier and Joris, Bernard and Gobec, Stanislav and D'hooghe, Matthias},
  issn         = {0947-6539},
  journal      = {CHEMISTRY-A EUROPEAN JOURNAL},
  keywords     = {antibiotics,biological activity,chiral pool,drug design,lactams,BETA-LACTAMASE INHIBITORS,ESCHERICHIA-COLI,BIOLOGICAL EVALUATION,CONVENIENT SYNTHESIS,LEAVING GROUP,D-ALANINE,ANTIBIOTICS,CEPHALOSPORINS,CHEMISTRY,ACIDS},
  language     = {eng},
  number       = {57},
  pages        = {15254--15266},
  title        = {In silico design and enantioselective synthesis of functionalized monocyclic 3-amino-1-carboxymethyl-β-lactams as inhibitors of penicillin-binding proteins of resistant bacteria},
  url          = {http://dx.doi.org/10.1002/chem.201801868},
  volume       = {24},
  year         = {2018},
}

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