Petra Štefanič Anderluh,1,* Gregor Vilfan,1 Andrej Preželj1 and Uroš Urleb1
1 Lek Pharmaceuticals d.d., Drug Discovery, Verovškova 57, SI-1526 Ljubljana, Slovenia
* Corresponding author: E-mail: petra.stefanic@sandoz.com
Phone: +386-1-580-2469
Abstract
The development of novel β-lactamase inhibitors with activity against various
clinically relevant β-lactamase producing
strains is one of the most important strategies to sustain the clinical efficacy
of β-lactam antibiotics. With intention to
eliminate antibiotic activity of meropenem with preserved activity against
β-lactamases C6-hydroxyethyl side chain of
meropenem was transformed to C6-ethylidene moiety. IC50 values of C6-ethylidene
derivative of meropenem were in
low mM range against TEM-1, SHV-1 and AmpC enzymes and were clearly inferior to
meropenem. Surprisingly, some
of the antimicrobial activity of meropenem was preserved implying that
C6-hydroxyethyl side chain is not essential to
retain antibiotic activity of meropenem.
Keywords: Tricyclic carbapenem, antimicrobial, β-lactamase inhibitor