Developing pyrazole-oxadiazole conjugates as potent anti-tubercular agents: an <i>in silico</i> and <i>in vitro</i> approach.

ABSTRACT: Decaprenylphosphoryl-beta-d-ribose 2'-oxidase (DprE1) is a unique enzyme in Mycobacterium tuberculosis (Mtb) essential for the synthesis of the cell wall constituent arabinan. It converts decaprenyl phosphoryl ribose (DPR) to decaprenyl phosphoryl arabinose (DPA) with DprE2. Inhibition of DprE1 affects the integrity of the cellular membrane, causing cell wall rupture, leakage of cellular contents, and ultimately, cell death. Structural analysis of the DprE1 binding site reveals three binding regions: hydrophobic head region, planar core nucleus, and solvent-accessible tail region. Based on these structural features and reported inhibitors, structure-based drug design (SBDD) was employed to design and develop 22 novel pyrazole-oxadiazole conjugates (PO1-PO22), combining a hydrophobic

SUBMITTER: Kumar SA 

PROVIDER: S-EPMC12694745 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature