College of Pharmacy, University of Nebraska Medical Center, Nebraska Medical Center, Omaha, Nebraska 986125, United States.
Department of Medical Parasitology and Infection Biology, Swiss Tropical Institute, Socinstrasse 57, Basel CH-4002, Switzerland.
J Med Chem. 2024 Oct 24;67(20):18235-18246. doi: 10.1021/acs.jmedchem.4c01532. Epub 2024 Oct 8.
We discovered medium-ring keto bislactams as a new antischistosomal chemotype. The ketone functional group and isoindolinone substructure were required for high antischistosomal activity. Aryl substitution with EWG functional groups decreased the chemical stability. These compounds were relatively polar with the measured LogD values ranging from <0 to 2.4, had kinetic aqueous solubilities between 40 and >320 μM, and had relatively low cytotoxicities with IC ranging from 52 to >390 μM. We identified two compounds with IC values < 5 μM against ex vivo ().
我们发现了中环酮双内酰胺类化合物，这是一种新型的抗血吸虫化学类型。酮官能团和异吲哚啉酮结构是抗血吸虫活性所必需的。具有 EWG 官能团的芳基取代会降低化合物的化学稳定性。这些化合物具有一定的极性，其 LogD 值范围为 <0 至 2.4，动力学水溶解度在 40 至 >320 μM 之间，细胞毒性相对较低，IC 值范围为 52 至 >390 μM。我们鉴定出两种对离体（）具有 IC 值<5 μM 的化合物。
