C4-alkylthiols with activity against Moraxella catarrhalis and Mycobacterium tuberculosis.
Kostova MB, Myers CJ, Beck TN, Plotkin BJ, Green JM, Boshoff HI, Barry CE, Deschamps JR, Konaklieva MI.
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.