Table 1.
New drug-target associations disclosed in the present study.
| Drug (brand names) | Drug category(ies) | Toxicity | Leishmania target(s) ID | Identity to (E-value) | TDRT druggability |
|---|---|---|---|---|---|
| Lonidamine (Doridamina) | Anticancer, antitrypanosomal | NA | Hexokinase, putative LbrM.21.0310 |
Hexokinase D (3E − 54) |
NA |
|
| |||||
| POLYSIN | Antiprotozoal | NA | ATP-dependent phosphofructokinase LbrM.29.2480 | Pyrophosphate-dependent phosphofructokinase (2.00E − 06) |
NA |
|
| |||||
| Saframycin A | Anticancer | NA | Glyceraldehyde 3-phosphate dehydrogenase LbrM.30.2950 |
Glyceraldehyde 3-phosphate dehydrogenase, muscle 2E − 91 |
NA |
|
| |||||
| Nadide | Chagas disease, parasitic diseases, and sleeping sickness | No reports of overdose; however, high doses of NADH (10 mg a day or more) may cause jitteriness, anxiety, and insomnia | Glycerol-3-phosphate dehydrogenase LbrM.10.0640 |
Glycerol-3-phosphate dehydrogenase [NAD+], cytoplasmic 2E − 31 |
0.2 |
|
| |||||
| Sulfacetamide; sulfanilamide; sulfoxone |
Bacterial infections | Oral LD50 mouse: 16500 mg/kg. Side effects include moderate to severe erythema (redness) and moderate edema (raised skin), nausea, vomiting, headache, dizziness, and tiredness. Higher exposure causes unconsciousness | Phosphomannose isomerase (PMI) LbrM.32.1750 |
Mannose-6-phosphate isomerase 3E − 59 |
0.6 |
|
| |||||
| Morantel tartrate, oxantel pamoate, and thiabendazole | Helicobacter pylori infection, Mature gastrointestinal nematode infections, Trichuris trichiura infection | Overdosage may be associated with transient disturbances of vision and psychic alterations | NADH-dependent fumarate reductase LbrM.34.0820 | Fumarate reductase flavoprotein subunit 2.00E − 13 | 0.5 |
|
| |||||
| CEPHARANTHINE; CONESSINE | African trypanosomiasis; Chagas disease; Leishmania infections; parasitic diseases; | NA | Trypanothione reductase LmjF05.0350 |
Glutathione reductase, mitochondrial 6E − 65 |
NA |
|
| |||||
| Aciglut, Glusate, Glutacid, Glutamicol, Glutamidex, Glutaminol, and Glutaton |
Antibacterial; antitrypanosomal | Glutamate causes neuronal damage and eventual cell death, particularly when the NMDA receptors are activated. High dosages of glutamic acid may include symptoms such as headaches and neurological problems | Aspartate aminotransferase, putative LbrM.24.0370 | Aspartate aminotransferase, mitochondrial 8E − 89 |
0.3 |
|
| |||||
| 2-Oxopropanoic acid, pyroracemic acid, and acetylformic acid | Bacterial infections | Pyruvate kinase LbrM.34.0010 |
Pyruvate kinase 1.00E − 117 |
NA | |
|
| |||||
| Succinic acid (Katasuccin, Kyselina jantarova) | NA | Oral rat LD50: 2260 mg/kg | Succinate dehydrogenase LmjF15.0990 |
Succinate dehydrogenase [ubiquinone] iron-sulfur subunit, mitochondrial 2E − 28 |
NA |
|
| |||||
| Adenovite, Cardiomone, Lycedan, My-B-Den, Phosaden, and Phosphaden | NA | NA | Acetyl-coenzyme A synthetase, putative LbrM.23.0580 |
Acetyl-coenzyme A synthetase, cytoplasmic 3E − 159 |
0.2 |