Department of Chemistry, American University, Washington, DC 20016, USA.
Bioorg Med Chem. 2011 Nov 15;19(22):6842-52. doi: 10.1016/j.bmc.2011.09.030. Epub 2011 Oct 1.
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.
抗菌药物耐药性对医疗保健构成全球性威胁。由于耐药微生物的出现，充分治疗传染病的能力日益受到威胁。特别需要新的药物开发方法来针对由于表达β-内酰胺酶而表现出广泛抗生素耐药性的生物体，β-内酰胺酶是细菌对β-内酰胺类抗生素产生耐药性的最常见机制。我们设计并合成了 20 种新型的含有烷基和芳基硫基的单环β-内酰胺化合物，并在 C4 位进行了修饰，随后测试了它们的抗菌活性。这些化合物对产生丝氨酸β-内酰胺酶的结核分枝杆菌野生型菌株（Mtb）和多种（n=6）产生β-内酰胺酶的卡他莫拉菌临床分离株具有内在活性。
