Synthesis and evaluation of Trehalose-Pks13 inhibitor conjugates targeting mycobacteria.

ABSTRACT: One obstacle to developing new drugs targeting Mycobacterium tuberculosis (Mtb) is its unique cell wall, which forms a significant permeability barrier to drug transport. Recently, transporters of trehalose and other disaccharides within this structure have been identified. We hypothesized that conjugating small molecules active against Mtb with trehalose could facilitate selective uptake of the trehalose conjugate into the cell. This strategy might enhance penetration of the hydrophobic mycomembrane or enable selective targeting of mycobacteria. To test this hypothesis, we used Cu(I)-catalyzed azide-alkyne Huisgen cycloaddition to conjugate 6-azido trehalose to known polyketide synthase 13 (Pks13) inhibitors, such as 2-aminothiophenes (AT), and benzofurans (BzF) with alkyne moieties, and

SUBMITTER: Kumbalathara A D USS 

PROVIDER: S-EPMC12406997 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature