Nonhydrolyzable d‑phenylalanine-benzoxazole derivatives retain antitubercular activity. (15th January 2023)

• Record Type: Journal Article
• Authors: Pepi, Michael J.; Chacko, Shibin; Kopetz, Nicole; Boshoff, Helena I.M.; Cuny, Gregory D.; Hedstrom, Lizbeth
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 80(2023)
• Publication Date: 2023-01-15
• Subjects: Tuberculosis -- PanG -- Ketopantoate reductase; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2022.129116
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: The emergence of drug resistant Mycobacterium tuberculosis, the causative agent of tuberculosis, demands the development of new drugs and new drug targets. We have recently reported that the d -phenylalanine benzoxazole Q112 has potent antibacterial activity against this pathogen with a distinct mechanism of action from other antimycobacterial agents. Q112 and previously reported derivatives were unstable in plasma and no free compound could be observed. Here we expand the structure-activity relationship for antimycobacterial activity and find nonhydrolyzable derivatives with decreased plasma binding. We also show that there is no correlation between antibacterial activity and inhibition of PanG, a putative target for these compounds.