Promiscuous Targets for Antitubercular Drug Discovery: The Paradigm of DprE1 and MmpL3
Abstract
:1. The Added Value of Promiscuous Targets for Antitubercular Drug Discovery
2. The First Discovery of DprE1 and MmpL3 as Drug Target
3. DprE1: The Hot TB Target of the Moment
3.1. Why DprE1 Is a Promiscuous Target
3.2. DprE1 Inhibitors, Which Are the Current Status and Future Perspectives
3.3. DprE2: A Promising Target for Future Drug Discovery
4. Mmpl3 Transporter: The Other Hot TB Target of the Moment
4.1. MmpL3: A Mycolic Acid Transporter
4.2. MmpL3: The Achilles Heel of Mycobacterium Tuberculosis
5. Future Perspectives for DprE1 and MmpL3 Inhibitors in Clinical Therapy
Author Contributions
Funding
Conflicts of Interest
References
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Chemical Class | Compound | Structure | M. tuberculosis MIC | Ref. |
---|---|---|---|---|
Covalent inhibitors | ||||
Benzothiazinones | BTZ043 | | 0.0023 µM | [30] |
PBTZ169 | | 0.001 µM | [49] | |
Dinitrobenzamides | DNB1 | | 0.69 µM | [32] |
Nitro-quinoxalines | VI-9376 | | 3.1 µM | [33] |
Triazoles | 377790 | | 0.48 µM | [51] |
Noncovalent inhibitors | ||||
Benzothiazoles | TCA1 | | 0.51 µM | [55] |
7a | | 0.08 µM | [61] | |
Thiadiazoles | GSK-710 | | 4 µM | [42] |
Carboxy-quinoxalines | Ty38c | | 3.1 µM | [58] |
Aminoquinolones | 3 | | 0.8 µM | [62] |
Pyrazolopyridones | 19 | | 0.1 µM | [63] |
Azaindoles | TBA-7371 | | 0.01 µM | [64] |
Chemical Class | Compound | Structure | M. tuberculosis MIC | Ref. |
---|---|---|---|---|
Diarylpyrroles | BM212 | | 3.6 µM | [36] |
1,2-diamine derivatives | DA5 | | 9.97 µM | [37] |
SQ109 | | 0.78 µM | [37] | |
Adamantyl urea | AU1235 | | 0.3 µM | [38] |
Benzimidazoles | C215 | | 16.0 µM | [51] |
Indolcarboxamides | NIDT349 | | 0.023 µM | [93] |
Tetrahydropyrazolo pyrimidine | THP P | | 0.3 µM | [94] |
Dihydrospiro[piperidine-4,4′-thieno[3,2-c]pyrans] | Spiro | | 0.3 µM | [94] |
Piperidinols | PIPD1 | | 1.28 µM | [95] |
Acetamides | E11 | | 8.0 µM | [96] |
Carboxamides | HC2091 | | 19.3 µM | [97] |
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Degiacomi, G.; Belardinelli, J.M.; Pasca, M.R.; De Rossi, E.; Riccardi, G.; Chiarelli, L.R. Promiscuous Targets for Antitubercular Drug Discovery: The Paradigm of DprE1 and MmpL3. Appl. Sci. 2020, 10, 623. https://doi.org/10.3390/app10020623
Degiacomi G, Belardinelli JM, Pasca MR, De Rossi E, Riccardi G, Chiarelli LR. Promiscuous Targets for Antitubercular Drug Discovery: The Paradigm of DprE1 and MmpL3. Applied Sciences. 2020; 10(2):623. https://doi.org/10.3390/app10020623
Chicago/Turabian StyleDegiacomi, Giulia, Juan Manuel Belardinelli, Maria Rosalia Pasca, Edda De Rossi, Giovanna Riccardi, and Laurent Roberto Chiarelli. 2020. "Promiscuous Targets for Antitubercular Drug Discovery: The Paradigm of DprE1 and MmpL3" Applied Sciences 10, no. 2: 623. https://doi.org/10.3390/app10020623
APA StyleDegiacomi, G., Belardinelli, J. M., Pasca, M. R., De Rossi, E., Riccardi, G., & Chiarelli, L. R. (2020). Promiscuous Targets for Antitubercular Drug Discovery: The Paradigm of DprE1 and MmpL3. Applied Sciences, 10(2), 623. https://doi.org/10.3390/app10020623