Propenylamide and propenylsulfonamide cephalosporins as a novel class of anti-MRSA beta-lactams.
Novel C(3) propenylamide and propenylsulfonamide cephalosporins have been synthesized and tested for their ability to inhibit the penicillin-binding protein 2' (PBP2') from Staphylococcus epidermidis and the growth of a panel of clinically relevant bacterial species, including methicillin-resistant Staphylococcus aureus (MRSA). The most potent compounds inhibited the growth of MRSA strains with minimum inhibitory concentrations (MIC) as low as 1 microg/mL. The structure-activity relationship revealed the potential for further optimization of this new cephalosporin class.
Pohlmann
Jens
J
Basilea Pharmaceutica International Ltd, CH-4005 Basel, Switzerland. jens.pohlmann@basilea.com
Vasilevich
Natalya I
NI
Glushkov
Andrei I
AI
Kellenberger
Laurenz
L
Shapiro
Stuart
S
Caspers
Patrick
P
Page
Malcolm G P
MG
Danel
Franck
F
D000577:Amides / Q000737:chemistry*; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D002511:Cephalosporins / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects* / Q000201:enzymology; D008826:Microbial Sensitivity Tests; D013329:Structure-Activity Relationship; D047090:beta-Lactams / Q000037:antagonists & inhibitors* / Q000378:metabolism
D000577:Amides; D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D047090:beta-Lactams