Beck Tim N, Lloyd Dina, Kuskovsky Rostislav, Minah Jeanette, Arora Kriti, Plotkin Balbina J, Green Jacalyn M, Boshoff Helena I, Barry Clifton, Deschamps Jeffrey, Konaklieva Monika I
Department of Chemistry, American University, Washington, DC 20016, USA.
Tuberculosis Research Section, LCID, NIAID, NIH 33 North Drive, Bldg 33, Rm 2W20C, Bethesda, MD 20892, USA.
Bioorg Med Chem. 2015 Feb 1;23(3):632-47. doi: 10.1016/j.bmc.2014.11.025. Epub 2014 Dec 12.
The prevalence of drug resistance in both clinical and community settings as a consequence of alterations of biosynthetic pathways, enzymes or cell wall architecture is a persistent threat to human health. We have designed, synthesized, and tested a novel class of non-transpeptidase, β-lactamase resistant monocyclic β-lactams that carry an arylthio group at C4. These thioethers exhibit inhibitory and cidal activity against serine β-lactamase producing Mycobacterium tuberculosis wild type strain (Mtb) and multiple (n=8) β-lactamase producing Moraxella catarrhalis clinical isolates.
由于生物合成途径、酶或细胞壁结构改变，临床和社区环境中耐药性的普遍存在对人类健康构成持续威胁。我们设计、合成并测试了一类新型的非转肽酶、耐β-内酰胺酶的单环β-内酰胺类药物，其在C4位带有芳硫基。这些硫醚对产生丝氨酸β-内酰胺酶的结核分枝杆菌野生型菌株（Mtb）以及多种（n = 8）产生β-内酰胺酶的卡他莫拉菌临床分离株具有抑制和杀菌活性。
