Pharmacophore mapping of the crucial mediators of dual inhibitor activity of PanK and PyrG in tuberculosis disease

Tuberculosis (TB) is an infection caused by Mycobacterium tuberculosis, responsible for 1.66 million documented deaths in 2020. The increase in reported cases of M. tuberculosis resistance to the main drugs shows the need to develop new and efficient drugs for better TB control. A strategy to overco...

Full description

Saved in:
Bibliographic Details
Published in:Molecular simulation 2022-03, Vol.48 (5), p.403-416
Main Authors: Ejalonibu, Murtala A., Elrashedy, Ahmed A., Lawal, Monsurat M., Mhlongo, Ndumiso N., Kumalo, Hezekiel M.
Format: Article
Language:English
Subjects:
Drugs
Energy value
Free energy
Kinases
molecular dynamics simulations
PanK
pharmacophore design
PyrG
Screening
Tuberculosis
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Tuberculosis (TB) is an infection caused by Mycobacterium tuberculosis, responsible for 1.66 million documented deaths in 2020. The increase in reported cases of M. tuberculosis resistance to the main drugs shows the need to develop new and efficient drugs for better TB control. A strategy to overcome the resistance problem could be the polypharmacology approach, whereby researchers develop a single molecule that acts on different targets. Polypharmacology could have features that make it more effective than classical polypharmacy, in which investigators pull various drugs with high affinity for one target together. Based on the effectiveness of multitargeting, this work aimed to use combined in silico techniques to identify potential dual inhibitors for Pantothenate Kinases (PanK) and CTP synthetase PyrG. In silico drug design allows for screening of potential leads, thus decreasing time and resource consumption. This study demonstrates an optimised and proven screening technique to discover a potential small-molecule inhibitor of Mycobacterium tuberculosis PanK and PyrG. The favourable binding free energy values and interaction profiles show ZINC53995076 as a potent dual inhibitor of the Mycobacterium tuberculosis PanK and PyrG.
ISSN:0892-7022
1029-0435
DOI:10.1080/08927022.2021.2019251