- Synthesis of a leopolic acid-inspired tetramic acid with antimicrobial activity against multidrug-resistant bacteria
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The increasing emergence of multidrug-resistant pathogens is one of the biggest threats to human health and food security. The discovery of new antibacterials, and in particular the finding of new scaffolds, is an imperative goal to stay ahead of the evolution of antibiotic resistance. Herein we report the synthesis of a 3-decyltetramic acid analogue of the ureido dipeptide natural antibiotic leopolic acid A. The key step in the synthetic strategy is an intramolecular Lacey-Dieckmann cyclization reaction of a linear precursor to obtain the desired 3-alkyl-substituted tetramic acid core. The synthesized analogue is more effective than the parent leopolic acid A against Gram-positive (Staphylococcus pseudintermedius) and Gram-negative (E. coli) bacteria (MIC 8 μg/mL and 64 μg/mL, respectively). Interestingly, the compound shows a significant activity against Staphylococcus pseudintermedius strains expressing a multidrug-resistant phenotype (average MIC 32 μg/mL on 30 strains tested). These results suggest that this molecule can be considered a promising starting point for the development of a novel class of antibacterial agents active also against resistant strains.
- Mattio, Luce,Musso, Loana,Scaglioni, Leonardo,Pinto, Andrea,Martino, Piera Anna,Dallavalle, Sabrina
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supporting information
p. 2482 - 2487
(2018/10/04)
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- REMEDY FOR DIABETES
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A method of screening a compound having a hypoglycemic effect (hereinafter referred to as "hypoglycemic compound"), a remedy for diabetes which contains a compound having a novel function mechanism, etc. More specifically speaking, a method of screening a hypoglycemic compound capable of binding to the β subunit of a trimeric GTP-binding protein, a remedy for diabetes comprising a hypoglycemic compound, which is characterized by being capable of binding to the β subunit of a trimeric GTP-binding protein, as the active ingredient, etc.
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Page/Page column 22
(2010/04/23)
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