Advanced piperazine-containing inhibitors target microbial β-glucuronidases linked to gut toxicity

• DOI: 10.1039/d4cb00058g
• Publication Date: 2024-07-16T08:31:25Z
• Authors: Amanda L. Graboski; Joshua B. Simpson; Samuel J. Pellock; Naimee Mehta; Benjamin C. Creek...; Yamuna Ariyarathna; Aadra P. Bhatt; Parth B. Jariwala; Josh J. Sekela; Mark E. Kowalewski; Natalie K. Barker; Angie L. Mordant; Valentina B. Borl...; Hermen Overkleeft; Laura E. Herring; Jian Jin; Lindsey I. James; Matthew R. Redinbo
• Keywords: 0301 basic medicine; Chemistry; 03 medical and health sciences

Leveraging medicinal chemistry and structural biology to optimize microbial GUS inhibitors to UNC10206581, which displays potent L1 and FMN GUS activity – the structural subclasses linked to GI toxicity via small molecule glucuronide reactivation.