In Silico Search of Energy Metabolism Inhibitors for Alternative Leishmaniasis Treatments

Table 1

New drug-target associations disclosed in the present study.

Drug (brand names)	Drug category(ies)	Toxicity	Leishmania target(s) ID	Identity to (-value)	TDRT druggability
Lonidamine (Doridamina)	Anticancer, antitrypanosomal	NA	Hexokinase, putative; LbrM.21.0310	Hexokinase D; ()	NA
POLYSIN	Antiprotozoal	NA	ATP-dependent phosphofructokinase LbrM.29.2480	Pyrophosphate-dependent phosphofructokinase; ()	NA
Saframycin A	Anticancer	NA	Glyceraldehyde 3-phosphate dehydrogenase; LbrM.30.2950	Glyceraldehyde 3-phosphate dehydrogenase, muscle	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	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	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	0.5
CEPHARANTHINE; CONESSINE	African trypanosomiasis; Chagas disease; Leishmania infections; parasitic diseases;	NA	Trypanothione reductase; LmjF05.0350	Glutathione reductase, mitochondrial	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	0.3
2-Oxopropanoic acid, pyroracemic acid, and acetylformic acid	Bacterial infections		Pyruvate kinase; LbrM.34.0010	Pyruvate kinase	NA
Succinic acid (Katasuccin, Kyselina jantarova)	NA	Oral rat LD50: 2260 mg/kg	Succinate dehydrogenase; LmjF15.0990	Succinate dehydrogenase [ubiquinone] iron-sulfur subunit, mitochondrial	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	0.2