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 beta-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-beta-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 b-lactams
were shown to be valuable antibacterial agents against
selected linezolid-resistant strains, with a minimum inhibitory
concentrations of 2–4 mgL-1
