Promiscuous Targets for Antitubercular Drug Discovery: The Paradigm of DprE1 and MmpL3
The development and spread of <i>Mycobacterium tuberculosis</i> multi-drug resistant strains still represent a great global health threat, leading to an urgent need for novel anti-tuberculosis drugs. Indeed, in the last years, several efforts have been made in this direction, through a n...
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MDPI AG
2020-01-01
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| Series: | Applied Sciences |
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| Online Access: | https://www.mdpi.com/2076-3417/10/2/623 |
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| author | Giulia Degiacomi Juan Manuel Belardinelli Maria Rosalia Pasca Edda De Rossi Giovanna Riccardi Laurent Roberto Chiarelli |
| author_facet | Giulia Degiacomi Juan Manuel Belardinelli Maria Rosalia Pasca Edda De Rossi Giovanna Riccardi Laurent Roberto Chiarelli |
| author_sort | Giulia Degiacomi |
| collection | DOAJ |
| description | The development and spread of <i>Mycobacterium tuberculosis</i> multi-drug resistant strains still represent a great global health threat, leading to an urgent need for novel anti-tuberculosis drugs. Indeed, in the last years, several efforts have been made in this direction, through a number of high-throughput screenings campaigns, which allowed for the identification of numerous hit compounds and novel targets. Interestingly, several independent screening assays identified the same proteins as the target of different compounds, and for this reason, they were named “promiscuous” targets. These proteins include DprE1, MmpL3, QcrB and Psk13, and are involved in the key pathway for <i>M. tuberculosis</i> survival, thus they should represent an Achilles’ heel which could be exploited for the development of novel effective drugs. Indeed, among the last molecules which entered clinical trials, four inhibit a promiscuous target. Within this review, the two most promising promiscuous targets, the oxidoreductase DprE1 involved in arabinogalactan synthesis and the mycolic acid transporter MmpL3 are discussed, along with the latest advancements in the development of novel inhibitors with anti-tubercular activity. |
| first_indexed | 2024-12-10T17:23:27Z |
| format | Article |
| id | doaj.art-3cc1e615150247c5aafc1aab2ec6cd70 |
| institution | Directory Open Access Journal |
| issn | 2076-3417 |
| language | English |
| last_indexed | 2024-12-10T17:23:27Z |
| publishDate | 2020-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Applied Sciences |
| spelling | doaj.art-3cc1e615150247c5aafc1aab2ec6cd702022-12-22T01:39:54ZengMDPI AGApplied Sciences2076-34172020-01-0110262310.3390/app10020623app10020623Promiscuous Targets for Antitubercular Drug Discovery: The Paradigm of DprE1 and MmpL3Giulia Degiacomi0Juan Manuel Belardinelli1Maria Rosalia Pasca2Edda De Rossi3Giovanna Riccardi4Laurent Roberto Chiarelli5Department of Biology and Biotechnology “Lazzaro Spallanzani”, University of Pavia, 27100 Pavia, ItalyMycobacteria Research Laboratories, Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO 80523-1682, USADepartment of Biology and Biotechnology “Lazzaro Spallanzani”, University of Pavia, 27100 Pavia, ItalyDepartment of Biology and Biotechnology “Lazzaro Spallanzani”, University of Pavia, 27100 Pavia, ItalyDepartment of Biology and Biotechnology “Lazzaro Spallanzani”, University of Pavia, 27100 Pavia, ItalyDepartment of Biology and Biotechnology “Lazzaro Spallanzani”, University of Pavia, 27100 Pavia, ItalyThe development and spread of <i>Mycobacterium tuberculosis</i> multi-drug resistant strains still represent a great global health threat, leading to an urgent need for novel anti-tuberculosis drugs. Indeed, in the last years, several efforts have been made in this direction, through a number of high-throughput screenings campaigns, which allowed for the identification of numerous hit compounds and novel targets. Interestingly, several independent screening assays identified the same proteins as the target of different compounds, and for this reason, they were named “promiscuous” targets. These proteins include DprE1, MmpL3, QcrB and Psk13, and are involved in the key pathway for <i>M. tuberculosis</i> survival, thus they should represent an Achilles’ heel which could be exploited for the development of novel effective drugs. Indeed, among the last molecules which entered clinical trials, four inhibit a promiscuous target. Within this review, the two most promising promiscuous targets, the oxidoreductase DprE1 involved in arabinogalactan synthesis and the mycolic acid transporter MmpL3 are discussed, along with the latest advancements in the development of novel inhibitors with anti-tubercular activity.https://www.mdpi.com/2076-3417/10/2/623mycobacteriatuberculosismulti-drug resistancedrug discoverypromiscuous targets |
| spellingShingle | Giulia Degiacomi Juan Manuel Belardinelli Maria Rosalia Pasca Edda De Rossi Giovanna Riccardi Laurent Roberto Chiarelli Promiscuous Targets for Antitubercular Drug Discovery: The Paradigm of DprE1 and MmpL3 Applied Sciences mycobacteria tuberculosis multi-drug resistance drug discovery promiscuous targets |
| title | Promiscuous Targets for Antitubercular Drug Discovery: The Paradigm of DprE1 and MmpL3 |
| title_full | Promiscuous Targets for Antitubercular Drug Discovery: The Paradigm of DprE1 and MmpL3 |
| title_fullStr | Promiscuous Targets for Antitubercular Drug Discovery: The Paradigm of DprE1 and MmpL3 |
| title_full_unstemmed | Promiscuous Targets for Antitubercular Drug Discovery: The Paradigm of DprE1 and MmpL3 |
| title_short | Promiscuous Targets for Antitubercular Drug Discovery: The Paradigm of DprE1 and MmpL3 |
| title_sort | promiscuous targets for antitubercular drug discovery the paradigm of dpre1 and mmpl3 |
| topic | mycobacteria tuberculosis multi-drug resistance drug discovery promiscuous targets |
| url | https://www.mdpi.com/2076-3417/10/2/623 |
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