Identification of inhibitors targeting Mycobacterium tuberculosis cell wall biosynthesis via dynamic combinatorial chemistry. Issue 77 (14th September 2017)

• Record Type: Journal Article
• Authors: Fu, Jian; Fu, Huixiao; Dieu, Marc; Halloum, Iman; Kremer, Laurent; Xia, Yufen; Pan, Weidong; Vincent, Stéphane P.
• Is Part Of: Chemical communications. Volume 53:Issue 77(2017)
• Page Start: 10632
• Page End: 10635
• Publication Date: 2017-09-14
• Subjects: Chemistry -- Periodicals; 540
• DOI: 10.1039/c7cc05251k
• Languages: English
• ISSNs: 1359-7345

Abstract

Abstract : In this study, we report a dynamic combinatorial approach along with highly efficient in situ screening to identify inhibitors of UDP-galactopyranose mutase (UGM), an essential enzyme involved in mycobacterial cell wall biosynthesis. Abstract : In this study, we report a dynamic combinatorial approach along with highly efficient in situ screening to identify inhibitors of UDP-galactopyranose mutase (UGM), an essential enzyme involved in mycobacterial cell wall biosynthesis. These two technologies converged to the identification of a new UGM inhibitor chemotype. Importantly, the best molecule not only displayed high affinity for the target enzyme but also exhibited in vitro growth inhibition against whole Mycobacterium tuberculosis cells. The strategy described here provides an avenue to explore a novel inhibitor class for UGMs and paves the way for further pharmacological studies on tuberculosis treatment.