Table 2. Repurposed Anti-Infective Drugs against Tuberculosis, Their Mechanisms of Action, MICs, and Ongoing Investigationsa.
| S. no. | Drug name (Drug class) | Mechanism of action/Drug target in M.tb | Minimum inhibitory concentration (MIC) in M.tb | Current status/ongoing studies | Refs |
|---|---|---|---|---|---|
| Antibacterial drugs | |||||
| 1 | Gatifloxacin (Fluoroquinolone) | DNA-Gyrase | 0.5 mg/L | Phase I, II trials completed | NCT0039608449 |
| 2 | Metronidazole (Nitroimidazole) | Break DNA helical structure | 16 μg/mL or higher | Phase II trials completed | NCT00425113 |
| 3 | Doxycycline (Tetracycline) | Inhibit host MMPs and act as HDT | 200 mg/kgb MIC – 0.016 μg/mL | Phase II trials completed | NCT0277499345 |
| 4 | Sulfamethoxazole (Sulpha drugs) | Inhibits synthesis of dihydrofolic acid | 9.5 mg/L | Phase II trials completed | NCT0183298768 |
| 5 | Biapenem (Carbapenem) | Inhibit cell wall synthesis | 2.5–5 μg/mL | in vivo | (69) |
| 6 | Tebipenem (β-Lactams) | Inhibit cell wall synthesis | 1.25–2.5 μg/mL | in vivo | (33) |
| 7 | Minocycline (Tetracycline) | Bind to 30S ribosomal subunit, inhibit protein synthesis | MIC50 < 2 mg/L | in vitro and in vivo | (42) |
| 8 | Cefdinir (Cephalosporin) | Inhibit cell wall synthesis | 2–4 mg/L (H37Ra), 0.5 and 16 mg/L (clinical Isolates) | in vitro and in vivo | (38) |
| 9 | Cefpodoxime (Cephalosporin) | Inhibit cell wall synthesis | >128 μg/mL (without Calvulanate), 32 μg/mL (with Calvulanate) | in vitro and in vivo | (70) |
| 10 | Fusidic acid (Fusidane) | Inhibit translocation | 32–64 mg/L | in silico and in vitro | (71) |
| 11 | Lymecycline (Tetracycline) | TrpD, CoaA | 10–100 μg/mL(H37Rv) | in silico and in vitro | (43) |
| 12 | Cefazolin (Cephalosporin) | Bind penicillin binding proteins, halt peptidoglycan synthesis | 64 mg/L (H37Ra) and, 2–8 mg/L with15 mg/L avibactam | in vitro | (39) |
| 13 | Vancomycin (Glycopeptide) | Inhibit cell wall synthesis | 0.5 mg/L (H37Ra),3 mg/L (H37Rv)12–96 mg/L (MDR isolates) | in vitro | (47) |
| Antifungal Drugs | |||||
| 15 | Econazole (Azole) | Lanosterol 14 α-demethylase | MIC90- 4 μg/mL (M.tb clinical isolates) | in vitro, in vivo | (51) |
| 16 | Clomitrazole (Azole) | Lanosterol 14 α-demethylase | MIC90- 8 μg/mL (M.tb clinical isolates) | in vitro | (51) |
| 17 | Artemisinin | Membrane-associated protein | 75 μg/mL | in vitro | (53) |
| Anti-Protozoal Drugs | |||||
| 18 | Nitazoxanide (Thiazolide) | Disrupt membrane potential, pH homeostasis | 16 μg/mL (H37Rv),12 to 28 μg/mL (M.tb clinical isolates) | Phase II trials completed | NCT0268424072 |
| 19 | Chloroquine (Class 4-aminoquinoline) | Efflux pump inhibitor | NA | in silico, in vivo | (60) |
| 20 | Mefloquine (Quinine) | Interfere with mycolic acids biosynthesis | 4–16 μg/mL (M.tb clinical isolates) | in vitro | (73) |
| 21 | Tafenoquine (Quinine) | NA | 1.25–80 μM (MDR strain) | in vitro | (61) |
| 22 | Pyronaridine (Benzonaphthyridine) | Inhibit DNA synthesis | 5 μg/mL | in silico, in vitro | (58) |
| 23 | Ipronidazole (Nitroimidazole) | NA | 16 μg/mL (clinical isolates) | in vitro | (74) |
| Antiviral Drugs | |||||
| 24 | Isoprinosine | HDT against M.tb | NA | in vivo | (62) |
| 25 | Saquinavir | HDT against M.tb | 5 to 20 μg/mL | in vitro | (63) |
| Anti-Helminthic Drugs | |||||
| 26 | Pyrvinium pamoate (Naphthoic acid) | NA | 1.5 to 4.8 μg/mL (H37Rv, MDR isolates) | in vitro, in vivo | (75) |
| 27 | Ivermectin (Avermectin) | NA | 6 μg/mL (H37Rv) | in vitro | (64) |
| 28 | Selamectin (Avermectin) | NA | 3 μg/mL (H37Rv) | in vitro | (64,66) |
| 29 | Moxidectin (Avermectin) | NA | 3 μg/mL (H37Rv) | in vitro | (64) |
| 30 | Niclosamide | NA | 5 μM (BCG, Beijing) | in silico, in vitro | (76, 77) |
a
NA: Not available, CT: clinical trials.
b
Patient daily dosage.