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Overcoming Mycobacterium tuberculosis through small molecule inhibitors to break down cell wall synthesis

Mycobacterium tuberculosis (MTB) utilizes multiple mechanisms to obtain antibiotic resistance during the treatment of infections. In addition, the biofilms, secreted by MTB, can further protect the latter from the contact with drug molecules and immune cells. These self-defending mechanisms lay a fo...

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Autores principales: Kuang, Wenbin, Zhang, Haolin, Wang, Xiao, Yang, Peng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9366312/
https://www.ncbi.nlm.nih.gov/pubmed/35967276
http://dx.doi.org/10.1016/j.apsb.2022.04.014
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author Kuang, Wenbin
Zhang, Haolin
Wang, Xiao
Yang, Peng
author_facet Kuang, Wenbin
Zhang, Haolin
Wang, Xiao
Yang, Peng
author_sort Kuang, Wenbin
collection PubMed
description Mycobacterium tuberculosis (MTB) utilizes multiple mechanisms to obtain antibiotic resistance during the treatment of infections. In addition, the biofilms, secreted by MTB, can further protect the latter from the contact with drug molecules and immune cells. These self-defending mechanisms lay a formidable challenge to develop effective therapeutic agents against chronic and recurring antibiotic-tolerant MTB infections. Although several inexpensive and effective drugs (isoniazid, rifampicin, pyrazinamide and ethambutol) have been discovered for the treatment regimen, MTB continues to cause considerable morbidity and mortality worldwide. Antibiotic resistance and tolerance remain major global issues, and innovative therapeutic strategies are urgently needed to address the challenges associated with pathogenic bacteria. Gratifyingly, the cell wall synthesis of tubercle bacilli requires the participation of many enzymes which exclusively exist in prokaryotic organisms. These enzymes, absent in human hepatocytes, are recognized as promising targets to develop anti-tuberculosis drug. In this paper, we discussed the critical roles of potential drug targets in regulating cell wall synthesis of MTB. And also, we systematically reviewed the advanced development of novel bioactive compounds or drug leads for inhibition of cell wall synthesis, including their discovery, chemical modification, in vitro and in vivo evaluation.
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spelling pubmed-93663122022-08-12 Overcoming Mycobacterium tuberculosis through small molecule inhibitors to break down cell wall synthesis Kuang, Wenbin Zhang, Haolin Wang, Xiao Yang, Peng Acta Pharm Sin B Review Mycobacterium tuberculosis (MTB) utilizes multiple mechanisms to obtain antibiotic resistance during the treatment of infections. In addition, the biofilms, secreted by MTB, can further protect the latter from the contact with drug molecules and immune cells. These self-defending mechanisms lay a formidable challenge to develop effective therapeutic agents against chronic and recurring antibiotic-tolerant MTB infections. Although several inexpensive and effective drugs (isoniazid, rifampicin, pyrazinamide and ethambutol) have been discovered for the treatment regimen, MTB continues to cause considerable morbidity and mortality worldwide. Antibiotic resistance and tolerance remain major global issues, and innovative therapeutic strategies are urgently needed to address the challenges associated with pathogenic bacteria. Gratifyingly, the cell wall synthesis of tubercle bacilli requires the participation of many enzymes which exclusively exist in prokaryotic organisms. These enzymes, absent in human hepatocytes, are recognized as promising targets to develop anti-tuberculosis drug. In this paper, we discussed the critical roles of potential drug targets in regulating cell wall synthesis of MTB. And also, we systematically reviewed the advanced development of novel bioactive compounds or drug leads for inhibition of cell wall synthesis, including their discovery, chemical modification, in vitro and in vivo evaluation. Elsevier 2022-08 2022-04-27 /pmc/articles/PMC9366312/ /pubmed/35967276 http://dx.doi.org/10.1016/j.apsb.2022.04.014 Text en © 2022 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Review
Kuang, Wenbin
Zhang, Haolin
Wang, Xiao
Yang, Peng
Overcoming Mycobacterium tuberculosis through small molecule inhibitors to break down cell wall synthesis
title Overcoming Mycobacterium tuberculosis through small molecule inhibitors to break down cell wall synthesis
title_full Overcoming Mycobacterium tuberculosis through small molecule inhibitors to break down cell wall synthesis
title_fullStr Overcoming Mycobacterium tuberculosis through small molecule inhibitors to break down cell wall synthesis
title_full_unstemmed Overcoming Mycobacterium tuberculosis through small molecule inhibitors to break down cell wall synthesis
title_short Overcoming Mycobacterium tuberculosis through small molecule inhibitors to break down cell wall synthesis
title_sort overcoming mycobacterium tuberculosis through small molecule inhibitors to break down cell wall synthesis
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9366312/
https://www.ncbi.nlm.nih.gov/pubmed/35967276
http://dx.doi.org/10.1016/j.apsb.2022.04.014
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