The emergence of multidrug-resistant bacterial strains is particularly important in chronic pathologies such as cystic fibrosis (CF), in which persistent colonization and selection of resistant strains is favored by the frequent and repeated use of antibacterial agents. Staphylococcus aureus is a common pathogen in CF patients that has an associated increased multidrug resistance. In previous studies we demonstrated that the presence of a 4-alkylidene side chain directly linked to a β-lactam appeared to strengthen the potency against S. aureus, especially against methicillin-resistant S. aureus (MRSA) strains. In the present study, 21 new 4-alkylidene-β-lactams were synthesized and evaluated for antibacterial activity. We designed the new compounds to have aryl, benzyl, or phenethyl-carbamate groups on the C3 hydroxyethyl side chain. We found a correlation between biological activity and the nitrogen substituent of the carbamate group, and two phenethyl-carbamate β-lactams were shown to be valuable antibacterial agents against selected linezolid-resistant strains, with a minimum inhibitory concentrations of 2–4 mg L−1.

Giacomini, D., Martelli, G., Piccichè, M., Calaresu, E., Cocuzza, C., Musumeci, R. (2017). Design and Synthesis of 4-Alkylidene-β-lactams: Benzyl- and Phenethyl-carbamates as Key Fragments to Switch on Antibacterial Activity. CHEMMEDCHEM, 12(18), 1525-1533 [10.1002/cmdc.201700307].

Design and Synthesis of 4-Alkylidene-β-lactams: Benzyl- and Phenethyl-carbamates as Key Fragments to Switch on Antibacterial Activity

Cocuzza, C;Musumeci, R
2017

Abstract

The emergence of multidrug-resistant bacterial strains is particularly important in chronic pathologies such as cystic fibrosis (CF), in which persistent colonization and selection of resistant strains is favored by the frequent and repeated use of antibacterial agents. Staphylococcus aureus is a common pathogen in CF patients that has an associated increased multidrug resistance. In previous studies we demonstrated that the presence of a 4-alkylidene side chain directly linked to a β-lactam appeared to strengthen the potency against S. aureus, especially against methicillin-resistant S. aureus (MRSA) strains. In the present study, 21 new 4-alkylidene-β-lactams were synthesized and evaluated for antibacterial activity. We designed the new compounds to have aryl, benzyl, or phenethyl-carbamate groups on the C3 hydroxyethyl side chain. We found a correlation between biological activity and the nitrogen substituent of the carbamate group, and two phenethyl-carbamate β-lactams were shown to be valuable antibacterial agents against selected linezolid-resistant strains, with a minimum inhibitory concentrations of 2–4 mg L−1.
Articolo in rivista - Articolo scientifico
Carbamates, Azetidinones, Antibiotics, Lactams, Resistant bacteria
English
23-lug-2017
2017
12
18
1525
1533
none
Giacomini, D., Martelli, G., Piccichè, M., Calaresu, E., Cocuzza, C., Musumeci, R. (2017). Design and Synthesis of 4-Alkylidene-β-lactams: Benzyl- and Phenethyl-carbamates as Key Fragments to Switch on Antibacterial Activity. CHEMMEDCHEM, 12(18), 1525-1533 [10.1002/cmdc.201700307].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/165005
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