DiPuma Thomas, Thabthimthong Teerana, Kelley Emma H, Konczak Katherine, Beulke Megan, Herbert Claire, S Habeeb Mohammad Thahani, Starus Anna, Nocek Boguslaw, Olsen Kenneth W, Holz Richard C, Becker Daniel P
Department of Chemistry and Biochemistry, Loyola University Chicago, 1032 West Sheridan Road, Chicago, IL 60660, USA.
Midwest Center for Structural Genomics and Structural Biology Center, Biosciences Division, Argonne National Laboratory, Argonne, IL 60439, USA.
Bioorg Med Chem Lett. 2023 Mar 1;83:129177. doi: 10.1016/j.bmcl.2023.129177. Epub 2023 Feb 9.
Based on a hit from a high-throughput screen, a series of phenyltetrazole amides was synthesized and assayed for inhibitory potency against DapE from Haemophilus influenzae (HiDapE). The inhibitory potency was modest but confirmed, with the most potent analog containing an aminothiazole moiety displaying an IC = 50.2 ± 5.0 μM. Docking reveals a potential binding mode wherein the amide carbonyl bridges both zinc atoms in the active site, and the tetrazole forms key hydrogen bonds with Arg330.
基于高通量筛选的一个命中结果，合成了一系列苯基四唑酰胺，并测定了它们对流感嗜血杆菌DapE（HiDapE）的抑制活性。抑制活性适中但得到了证实，最有效的类似物含有一个氨基噻唑部分，其IC50 = 50.2 ± 5.0 μM。对接显示了一种潜在的结合模式，其中酰胺羰基桥接活性位点中的两个锌原子，并且四唑与Arg330形成关键氢键。
