Tuberculosis Drug Discovery: A Decade of Hit Assessment for Defined Targets
More than two decades have elapsed since the publication of the first genome sequence of Mycobacterium tuberculosis (Mtb) which, shortly thereafter, enabled methods to determine gene essentiality in the pathogen. Despite this, target-based approaches have not yielded drugs that have progressed to cl...
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Frontiers Media S.A.
2021-03-01
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| Series: | Frontiers in Cellular and Infection Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcimb.2021.611304/full |
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doaj-a58dcef44f3d492db8b335bfb4af88ef2021-03-15T06:03:51ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882021-03-011110.3389/fcimb.2021.611304611304Tuberculosis Drug Discovery: A Decade of Hit Assessment for Defined TargetsSangmi OhLena TrifonovVeena D. YadavClifton E. BarryHelena I. BoshoffMore than two decades have elapsed since the publication of the first genome sequence of Mycobacterium tuberculosis (Mtb) which, shortly thereafter, enabled methods to determine gene essentiality in the pathogen. Despite this, target-based approaches have not yielded drugs that have progressed to clinical testing. Whole-cell screening followed by elucidation of mechanism of action has to date been the most fruitful approach to progressing inhibitors into the tuberculosis drug discovery pipeline although target-based approaches are gaining momentum. This review discusses scaffolds that have been identified over the last decade from screens of small molecule libraries against Mtb or defined targets where mechanism of action investigation has defined target-hit couples and structure-activity relationship studies have described the pharmacophore.https://www.frontiersin.org/articles/10.3389/fcimb.2021.611304/fulltuberculosisantitubercular agentstructure-activity relationshipdrug targetcell wallrespiration |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Sangmi Oh Lena Trifonov Veena D. Yadav Clifton E. Barry Helena I. Boshoff |
| spellingShingle |
Sangmi Oh Lena Trifonov Veena D. Yadav Clifton E. Barry Helena I. Boshoff Tuberculosis Drug Discovery: A Decade of Hit Assessment for Defined Targets Frontiers in Cellular and Infection Microbiology tuberculosis antitubercular agent structure-activity relationship drug target cell wall respiration |
| author_facet |
Sangmi Oh Lena Trifonov Veena D. Yadav Clifton E. Barry Helena I. Boshoff |
| author_sort |
Sangmi Oh |
| title |
Tuberculosis Drug Discovery: A Decade of Hit Assessment for Defined Targets |
| title_short |
Tuberculosis Drug Discovery: A Decade of Hit Assessment for Defined Targets |
| title_full |
Tuberculosis Drug Discovery: A Decade of Hit Assessment for Defined Targets |
| title_fullStr |
Tuberculosis Drug Discovery: A Decade of Hit Assessment for Defined Targets |
| title_full_unstemmed |
Tuberculosis Drug Discovery: A Decade of Hit Assessment for Defined Targets |
| title_sort |
tuberculosis drug discovery: a decade of hit assessment for defined targets |
| publisher |
Frontiers Media S.A. |
| series |
Frontiers in Cellular and Infection Microbiology |
| issn |
2235-2988 |
| publishDate |
2021-03-01 |
| description |
More than two decades have elapsed since the publication of the first genome sequence of Mycobacterium tuberculosis (Mtb) which, shortly thereafter, enabled methods to determine gene essentiality in the pathogen. Despite this, target-based approaches have not yielded drugs that have progressed to clinical testing. Whole-cell screening followed by elucidation of mechanism of action has to date been the most fruitful approach to progressing inhibitors into the tuberculosis drug discovery pipeline although target-based approaches are gaining momentum. This review discusses scaffolds that have been identified over the last decade from screens of small molecule libraries against Mtb or defined targets where mechanism of action investigation has defined target-hit couples and structure-activity relationship studies have described the pharmacophore. |
| topic |
tuberculosis antitubercular agent structure-activity relationship drug target cell wall respiration |
| url |
https://www.frontiersin.org/articles/10.3389/fcimb.2021.611304/full |
| work_keys_str_mv |
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