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