当前位置: X-MOL 学术ACS Infect. Dis. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Broad Spectrum β-Lactamase Inhibition by a Thioether Substituted Bicyclic Boronate.
ACS Infectious Diseases ( IF 5.3 ) Pub Date : 2019-12-16 , DOI: 10.1021/acsinfecdis.9b00330
Anete Parkova 1 , Anka Lucic 2 , Alen Krajnc 2 , Jürgen Brem 2 , Karina Calvopiña 2 , Gareth W Langley 2 , Michael A McDonough 2 , Peteris Trapencieris 1 , Christopher J Schofield 2
Affiliation  

β-Lactamases comprise the most widely used mode of resistance to β-lactam antibiotics. Cyclic boronates have shown promise as a new class of β-lactamase inhibitor, with pioneering potential to potently inhibit both metallo- and serine-β-lactamases. We report studies concerning a bicyclic boronate ester with a thioether rather than the more typical β-lactam antibiotic “C-6/C-7” acylamino type side chain, which is present in the penicillin/cephalosporin antibiotics. The thioether bicyclic boronate ester was tested for activity against representative serine- and metallo-β-lactamases. The results support the broad inhibition potential of bicyclic boronate based inhibitors with different side chains, including against metallo-β-lactamases from B1, B2, and B3 subclasses. Combined with previous crystallographic studies, analysis of a crystal structure of the thioether inhibitor with the clinically relevant VIM-2 metallo-β-lactamase implies that further SAR work will expand the already broad scope of β-lactamase inhibition by bicyclic boronates.

中文翻译:

硫醚取代的双环硼酸盐对广谱β-内酰胺酶的抑制作用。

β-内酰胺酶是对β-内酰胺类抗生素耐药的最广泛使用方式。环状硼酸盐已显示出有望作为新型的β-内酰胺酶抑制剂,具有潜在地有效抑制金属-和丝氨酸-β-内酰胺酶的开创性潜力。我们报道了有关双环硼酸酯与硫醚而不是青霉素/头孢菌素抗生素中存在的更典型的β-内酰胺抗生素“ C-6 / C-7”酰基氨基型侧链的研究。测试了硫醚双环硼酸酯对代表性的丝氨酸和金属β-内酰胺酶的活性。结果支持具有不同侧链的基于双环硼酸酯的抑制剂的广泛抑制潜力,包括针对来自B1,B2和B3亚类的金属β-内酰胺酶。结合以前的晶体学研究,
更新日期:2019-12-16
down
wechat
bug