Identification of DprE1 inhibitors for tuberculosis through integrated in-silico approaches

Decaprenylphosphoryl-β-D-ribose-2′-epimerase (DprE1), a crucial enzyme in the process of arabinogalactan and lipoarabinomannan biosynthesis, has become the target of choice for anti-TB drug discovery in the recent past. The current study aims to find the potential DprE1 inhibitors through in-silico...

Full description

Saved in:
Bibliographic Details
Published in:Scientific reports 2024-05, Vol.14 (1), p.11315-28, Article 11315
Main Authors: Dash, Swagatika, Rathi, Ekta, Kumar, Avinash, Chawla, Kiran, Kini, Suvarna G.
Format: Article
Language:English
Subjects:
3D-QSAR
631/114
631/154
639/638
Acrylamide
Alcohol Oxidoreductases
Antitubercular Agents - chemistry
Antitubercular Agents - pharmacology
Arabinogalactan
Bacterial Proteins - antagonists & inhibitors
Bacterial Proteins - chemistry
Bacterial Proteins - metabolism
Biosynthesis
Computer Simulation
D-Ribose
DprE1
Drug Discovery - methods
Enzyme Inhibitors - chemistry
Enzyme Inhibitors - pharmacology
Enzymes
Epimerase
Humanities and Social Sciences
Humans
Inhibitors
Molecular Docking Simulation
Molecular dynamics
Molecular Dynamics Simulation
multidisciplinary
Mycobacterium tuberculosis
Mycobacterium tuberculosis - drug effects
Mycobacterium tuberculosis - enzymology
Pharmacokinetics
Pharmacophore
Protein Binding
Quantitative Structure-Activity Relationship
Science
Science (multidisciplinary)
Structure-activity relationships
Tuberculosis
Tuberculosis - drug therapy
Citations: Items that this one cites
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Decaprenylphosphoryl-β-D-ribose-2′-epimerase (DprE1), a crucial enzyme in the process of arabinogalactan and lipoarabinomannan biosynthesis, has become the target of choice for anti-TB drug discovery in the recent past. The current study aims to find the potential DprE1 inhibitors through in-silico approaches. Here, we built the pharmacophore and 3D-QSAR model using the reported 40 azaindole derivatives of DprE1 inhibitors. The best pharmacophore hypothesis (ADRRR_1) was employed for the virtual screening of the chEMBL database. To identify prospective hits, molecules with good phase scores (> 2.000) were further evaluated by molecular docking studies for their ability to bind to the DprE1 enzyme (PDB: 4KW5). Based on their binding affinities (
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-024-61901-x