C4-alkylthiols with activity against Moraxella catarrhalis and Mycobacterium tuberculosis.
Antimicrobial resistance represents a global threat to healthcare. The ability to adequately treat infectious diseases is increasingly under siege due to the emergence of drug-resistant microorganisms. New approaches to drug development are especially needed to target organisms that exhibit broad antibiotic resistance due to expression of β-lactamases which is the most common mechanism by which bacteria become resistant to β-lactam antibiotics. We designed and synthesized 20 novel monocyclic β-lactams with alkyl- and aryl-thio moieties at C4, and subsequently tested these for antibacterial activity. These compounds demonstrated intrinsic activity against serine β-lactamase producing Mycobacterium tuberculosis wild type strain (Mtb) and multiple (n=6) β-lactamase producing Moraxella catarrhalis clinical isolates.
Department of Chemistry, American University, Washington, DC 20016, USA.
Maya B
MB
Kostova
Carey J
CJ
Myers
Tim N
TN
Beck
Balbina J
BJ
Plotkin
Jacalyn M
JM
Green
Helena I M
HI
Boshoff
Clifton E
CE
Barry
Jeffrey R
JR
Deschamps
Monika I
MI
Konaklieva
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D001936:Moraxella catarrhalis / Q000187:drug effects* / Q000201:enzymology; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000201:enzymology; D013438:Sulfhydryl Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001618:beta-Lactamases / Q000096:biosynthesis / Q000737:chemistry; D047090:beta-Lactams / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D013438:Sulfhydryl Compounds; D047090:beta-Lactams; D001618:beta-Lactamases