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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| Format: | Article |
| Language: | English |
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Elsevier
2022-08-01
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| Series: | Acta Pharmaceutica Sinica B |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211383522001873 |
| _version_ | 1798040982052143104 |
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| author | Wenbin Kuang Haolin Zhang Xiao Wang Peng Yang |
| author_facet | Wenbin Kuang Haolin Zhang Xiao Wang Peng Yang |
| author_sort | Wenbin Kuang |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-11T22:15:10Z |
| format | Article |
| id | doaj.art-275145496e9c4ab395bff1a76e35d7e3 |
| institution | Directory Open Access Journal |
| issn | 2211-3835 |
| language | English |
| last_indexed | 2024-04-11T22:15:10Z |
| publishDate | 2022-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Acta Pharmaceutica Sinica B |
| spelling | doaj.art-275145496e9c4ab395bff1a76e35d7e32022-12-22T04:00:24ZengElsevierActa Pharmaceutica Sinica B2211-38352022-08-0112832013214Overcoming Mycobacterium tuberculosis through small molecule inhibitors to break down cell wall synthesisWenbin Kuang0Haolin Zhang1Xiao Wang2Peng Yang3State Key Laboratory of Natural Medicines and Jiang Su Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China; Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, ChinaState Key Laboratory of Natural Medicines and Jiang Su Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China; Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, ChinaState Key Laboratory of Natural Medicines and Jiang Su Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China; Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, ChinaState Key Laboratory of Natural Medicines and Jiang Su Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China; Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China; Corresponding author.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.http://www.sciencedirect.com/science/article/pii/S2211383522001873Mycobacterium tuberculosisSmall molecule inhibitorCell wall synthesisAntibiotic resistance |
| spellingShingle | Wenbin Kuang Haolin Zhang Xiao Wang Peng Yang Overcoming Mycobacterium tuberculosis through small molecule inhibitors to break down cell wall synthesis Acta Pharmaceutica Sinica B Mycobacterium tuberculosis Small molecule inhibitor Cell wall synthesis Antibiotic resistance |
| 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 | Mycobacterium tuberculosis Small molecule inhibitor Cell wall synthesis Antibiotic resistance |
| url | http://www.sciencedirect.com/science/article/pii/S2211383522001873 |
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