UCL School of Pharmacy, 29-39 Brunswick Sq., London WC1N 1AX, UK.
UCL School of Pharmacy, 29-39 Brunswick Sq., London WC1N 1AX, UK.
Bioorg Med Chem. 2018 Jul 15;26(11):2921-2927. doi: 10.1016/j.bmc.2018.04.055. Epub 2018 Apr 27.
The rapid rise of antimicrobial resistance is one of the greatest challenges currently facing medical science. The most common cause of resistance to β-lactam antibiotics is the expression of β-lactamase enzymes, such as KPC-2. As such the development of novel inhibitors of KPC-2 and related enzymes is of the upmost importance. We report the design and synthesis of novel boronic acid transition state analogs containing a 1,4-substituted 1,2,3-triazole linker based on the known inhibitor 3-nitrophenyl boronic acid and demonstrate that they are promising scaffolds for the development inhibitors of KPC-2 with the ability to recover sensitivity to the antibiotic cefotaxime.
抗菌药物耐药性的迅速上升是目前医学科学面临的最大挑战之一。β-内酰胺类抗生素耐药性最常见的原因是β-内酰胺酶的表达，如 KPC-2。因此，开发新型 KPC-2 和相关酶的抑制剂至关重要。我们报告了基于已知抑制剂 3-硝基苯硼酸设计和合成新型硼酸过渡态类似物，这些类似物含有 1,4-取代的 1,2,3-三唑连接基，并证明它们是开发具有恢复对抗生素头孢噻肟敏感性的 KPC-2 抑制剂的有前途的支架。
