Design and Synthesis of New 4-Alkylidene-beta-lactams: Benzyl-and Phenethyl-carbamate as Key Fragments to Switch on the Antibacterial Activity.

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Design and Synthesis of New 4-Alkylidene-beta-lactams: Benzyl-and Phenethyl-carbamate as Key Fragments to Switch on the Antibacterial Activity.

ChemMedChem. 2017 Jul 23;:

Authors: Giacomini D, Martelli G, Piccichè M, Calaresu E, Cocuzza CEA, Musumeci R

Abstract
The emergence of multidrug resistant bacterial strains is particularly important in some chronic pathologies such as cystic fibrosis (CF), where persistent colonization and selection of resistant strains being favoured by the frequent and repeated use of antibacterial agents. Staphylococcus aureus is a common pathogen in CF patients with an associated increased multidrug resistance. In a previous research we demonstrated that the presence of a 4-alkylidene side chain directly linked to a beta-lactam appeared to strengthen the potency against S. aureus, expecially against MRSA strains. In the present study 21 new 4-alkyliden-beta-lactams were synthesized and evaluated for antibacterial activity. We designed the new molecules to have an aryl, benzyl, or phenethyl-carbamate groups on the C-3 hydroxyethyl side chain. We found a correlation between the biological activity and the N-substituent of the carbamate group, and phenethyl-carbamate beta-lactams 3s and t resulted being valuable antibacterials against some selected strains, comprising linezolid-resistant isolates, with a MIC potency of 2-4 mg/L.

PMID: 28737008 [PubMed - as supplied by publisher]

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