Table 3. Repurposed Non-Anti-Infective Drugs against Tuberculosis, Their Mechanism of Action, MICs, and Ongoing Investigationsa.
| S. no. | Drug name (Drug class) | Mechanism of action/Drug target in M.tb | Minimum inhibitory concentration (MIC) against M.tb | Current status/ongoing studies | Refs |
|---|---|---|---|---|---|
| NSAIDS (Anti-inflammatory Drugs) | |||||
| 1 | Meloxicam (Benzothiazine) | Cyclooxygenase-2 (COX-2) inhibitor | 7.5 mg for 8 weeksb | Phase III trial, results awaited | NCT02060006 |
| 2 | Aspirin (Acetylsalicylic acid) | Down-regulate the transcription and translation machinery | 3–20 mg/kg (murine model) | Phase II trial, results awaited | NCT0223736585,87 |
| 3 | Etoricoxib (Bipyridines) | Cyclooxygenase-2 (COX-2) inhibitor, used as HDT | NA | Phase I/II trial underway | NCT02503839128 |
| 4 | Ibuprofen (Propionic acid derivative) | InfB (Rv2839c) | 75 mg/L (H37Rv) | Phase II trials underway | NCT0278190984 |
| 5 | Celecoxib (Pyrazoles) | Efflux pump inhibitor | 16 μg/mL (M. smegmatis) ATCC 14468 | Phase I, trial completed | NCT02602509129 |
| 6 | Carprofen (2-Arylpropanoid acid) | Target the respiration process by disrupting membrane potential, inhibit drug efflux mechanism | 40 μg/mL or 146 μM (H37Rv) | in vitro | (90) |
| 7 | Diminazene (Phenylhydrazines) | MycP1 | 150 μM (58% inhibition) | Machine learning, in vitro | (91) |
| 8 | Ebselen (Benzoselenazole) | LdtMt2, cysA2, frdC, and glpD2 | 2.5 μg/mL | in vitro | (93, 94, 130) |
| 9 | Bromfenac (Benzophenone derivative) | Zmp1 and PDF | 100 μM | in vitro | (131) |
| 10 | Diflunisal (Salicylic acid derivative) | Zmp1 and PDF | 50 μM | in vitro | (131) |
| 11 | Oxyphenbutazone (Pyrazolidines) | Oxyphenbutazone converts into reactive species and deplete thiols and flavin nucleotides | 200 μM (H37Rv) | in vitro | (89) |
| Anticancer Drugs | |||||
| 12 | Fostamatinib (Kinase inhibitor) | Transmembrane Serine/Threonine-Protein Kinase B (Rv0014c, Rv0015c) | MIC50–7.98 μM | in silico, in vitro, in vivo | (132,133) |
| 13 | Elesclomol (Bis-thio-hydrazide amide) | Induce oxidative stress and generate ROS | 4 μg/mL | Knowledge-based and in vivo | (99) |
| 14 | Bis-biguanide dihydrochloride | NA | 0.05 μg/mL (clinical isolates) | in vitro, in vivo | (100) |
| 15 | Imatinib (Kinase inhibitor) | Increase myelopoiesis, phagosome maturation and acidification, autophagy in M.tb-infected mice and macrophages | 10 μM (H37Rv) | in vitro and in vivo | (96) |
| 16 | Gefitnib (Kinase inhibitor) | Increase lysosomal biogenesis and modulate cytokine signaling | 10 μM | in vitro and in vivo | (134) |
| 17 | Nilotinib (Kinase inhibitor) | Modulate autophagy in M. bovis infected macrophages, activation of PI3k/Akt/mTOR | 10 μM, 20 μM in M.bovis infected BMDM, RAW264.7, THP-1 cells | in vitro and in vivo | (135) |
| 18 | Bortezomib (Boronic acid derivative) | Caseinolytic proteases (ClpP1P2) | 4.3 μM | in vitro | (98) |
| 19 | Doxorubicin (Anthracycline) | MtbGyrB47 | IC50 range 2.1–4.7 μM | in silico and in vitro | (109,132) |
| 20 | Epirubicin (Anthracycline) | MtbGyrB47 | MIC90 –6.3 μM | in silico, in vitro | (109) |
| 21 | Idarubicin (Anthracycline) | MtbGyrB47 | MIC50 –4.7 μM | in silico, in vitro | (109) |
| 22 | Sorafenib | MtArgJ, FadD32 | MIC90 10 μg/mL | in silico, in vitro | (103,104) |
| Cardiovascular Drugs | |||||
| 23 | Pravastatin (Statins) | Stimulate host immune response. | 40 mg and Rifafour daily for 14 daysb EC50- 7.8 μM (M.tb infected macrophages) | Phase II trial underway | NCT03882177115 |
| 24 | Rosuvastatin (Statins) | Inhibit cellular cholesterol biosynthesis and induces autophagy | NA | Phase II trial in planning | NCT04504851115 |
| 25 | Verapamil (Phenylalkylamines) | Efflux pump, Ca2+ channel inhibitor, interferes with membrane energetics | 512 μM | Knowledge-based and in vivo | (136,137) |
| 26 | Simvastatin (Statins) | Inhibit de novo synthesis of cholesterol, induce autophagy in M.tb infected PBMC’s | 1, 20 μM (M.tb infected PBMC’s) | Knowledge-based and in vivo | (117) |
| 27 | Atorvastatin (Statins) | Inhibit cellular cholesterol biosynthesis, stimulates host immune response | EC75 - 2 μM (BCG infected THP cells) | in vivo studies | (138) |
| 28 | Fluvastatin (Statins) | Inhibit cellular cholesterol biosynthesis, stimulates host immune response | EC50 - 0.032 μM (M.tb infected macrophages) | in vivo | (115) |
| 29 | Cilostazol (Quinolinone derivative) | PDEi | 30 mg/kg dosage administered to mice models | in vivo studies | (139,140) |
| Anti-Psychotic Drugs | |||||
| 30 | Thioridazine (Phenothiazine derivative) | NDH-2, efflux pump inhibitor | 32 and 70 mg/kg (Balb/c Mouse model) | in vivo | (141) |
| 31 | Fluspirilene (Diphenylbutylpiperidine) | modulating the autophagic/lysosomal response | NA | in vitro and in vivo studies | (120) |
| 32 | Pimozide, (Diphenylbutylpiperidine) | modulating the autophagic/lysosomal response | NA | in vitro and in vivo studies | (120) |
| 33 | Chlorpromazine (Phenothiazine) | Inhibitor of efflux pump, K+ transport and | 47 μM (H37Rv) | in vitro studies | (136,142) |
| Anti-Parkinson Disease Drugs | |||||
| 34 | Entacopone (Nitrocatechol) | InhA | 205 μM (H37Rv) | in vitro | (123) |
| 35 | Tolcapone (Nitrocatechol) | InhA | 457 μM (H37Rv) | in vitro | (123) |
| Anti-Diabetic Drugs | |||||
| 36 | Metformin (Biguanide drug) | AMPK modulator, activate autophagy, target Rv0235c | 500–1000 mg orallyb | Phase I trials, in vivo | (124,125) NCT04930744 |
| 37 | Acarbose | murE, ppiB | 0.05–0.1 μg/mL | in vivo studies | (127,143) |
a
NA – Not available; CT – clinical trials.
b
Patient daily dosage.