Dear Spiral user, We’re pleased to introduce Helix, https://helix.imperial.ac.uk/ Imperial’s new repository for research datasets. Please use Helix for all future dataset deposits. There is no change to Spiral - continue depositing as usual. For queries, contact the Research Data Management team at rdm-enquiries@imperial.ac.uk. Kind regards, the Spiral Team. The Spiral team
Targeting the heart of Mycobacterium: advances in anti-tubercular agents disrupting cell wall biosynthesis
File(s)
pharmaceuticals-18-00070.pdf (4.44 MB)
Published version
Author(s)
Diab, Ahmad
Dickerson, Henry
Al Musaimi, Othman
Type
Journal Article
Abstract
Mycobacterium tuberculosis infections continue to pose a significant global health challenge, particularly due to the rise of multidrug-resistant strains, random mycobacterial mutations, and the complications associated with short-term antibiotic regimens. Currently, five approved drugs target cell wall biosynthesis in Mycobacterium tuberculosis. This review provides a comprehensive analysis of these drugs and their molecular mechanisms. Isoniazid, thioamides, and delamanid primarily disrupt mycolic acid synthesis, with recent evidence indicating that delamanid also inhibits decaprenylphosphoryl-β-D-ribose-2-epimerase, thereby impairing arabinogalactan biosynthesis. Cycloserine remains the sole approved drug that inhibits peptidoglycan synthesis, the foundational layer of the mycobacterial cell wall. Furthermore, ethambutol interferes with arabinogalactan synthesis by targeting arabinosyl transferase enzymes, particularly embB- and embC-encoded variants. Beyond these, six promising molecules currently in Phase II clinical trials are designed to target arabinan synthesis pathways, sutezolid, TBA 7371, OPC-167832, SQ109, and both benzothiazinone derivatives BTZ043 and PBTZ169, highlighting advancements in the development of cell wall-targeting therapies.
Date Issued
2025-01
Date Acceptance
2025-01-07
Citation
Pharmaceuticals, 2025, 18 (1)
URI
URL
DOI
ISSN
1424-8247
Publisher
MDPI AG
Journal / Book Title
Pharmaceuticals
Volume
18
Issue
1
Copyright Statement
© 2025 by the authors.
Licensee MDPI, Basel, Switzerland.
This article is an open access article
distributed under the terms and
conditions of the Creative Commons
Attribution (CC BY) license
(https://creativecommons.org/
licenses/by/4.0/).
License URL
Identifier
https://doi.org/10.3390/ph18010070
Publication Status
Published
Article Number
70
Date Publish Online
2025-01-09