Table 2.
Drug association for Chagas disease treatment.
| References | Drug association/original indication | Culture type/animal type | Main Results |
|---|---|---|---|
| Da Silva et al. (2012) | Itraconazole (Antifungal) and Benznidazole (Antiprotozoal) | Swiss albino mice, | Itraconazole alters the pharmacokinetic profile of benznidazole with accumulation in vivo, which represents a benefit as it provides the necessary dose reduction. |
| Perez-Mazliah et al. (2012) | Allopurinol (Antigout) and Benznidazole (Antiprotozoal) | Patients (human) | The sequential treatment with the drugs was well tolerated by the patients and considered viable. Immunological changes were detected giving benefits to patients with a disease in the chronic phase. |
| Valdez et al., 2012 | C4 (new drug) and Benznidazole (Antiprotozoal) | LLCMK2 and Balb/c mice | The association with C4 provided a reduction in the dose of benznidazole, achieving the same results as the usual dose. |
| Cencig et al., 2012 | Benznidazole and Nifurtimox, Posaconazole or Amphotericin B (Antiprotozoal; Antifungal) | Balb/c mice | The association of benznidazole with other drugs, in short periods, can cause the elimination of the parasite, except the association with amphotericin B. The association with nifurtimox led to the behavioral alteration of treated animals |
| Veiga-Santos et al., 2012 | Amiodarone (Antiarrhythmic) and Posaconazole (Antifungal) | ND* | The compounds interfered in the growth of the epimastigote form, in a dose-dependent manner. In all evolutionary forms, there are structural alterations in the parasite, with the formation of structures that indicate autophagy. |
| Diniz et al. (2013) | Benznidazole (Antiprotozoal) and Posaconazole (Antifungal) | Swiss mice | They presented synergism when administered together, being able to reduce the parasitemia to values inferior to those obtained with administration of the drugs alone. |
| Strauss et al. (2013) | Clomipramine (Antidepressant,Tricyclic) and Benznidazole (Antiprotozoal) | Swiss mice | Prevented cardiac conduction abnormalities in animals. In addition, the association prevented the formation of perivascular necrosis and inflammation in the liver |
| Martins et al. (2015) | Benznidazole (Antiprotozoal) and Itraconazole (Antifungal) | Swiss mice | The association of drugs led to less need for days of treatment, and reduced tissue damage caused by the disease in treated animals. |
| Herrera et al., 2017 | Simvastatin (Antihyperlipidemic) | Balb/c and sV/129 | In the murine model the association increases BNZ activity. Since 5-epi-lipoxin A4 induced by simvastatin treatment could improve the pathophysiological condition of patients. |
| Aguilera et al., 2017 | Benznidazole (Antiprotozoal) and Triosephosphate isomerase inhibitors, 2, 3, and 4. | Balb/c mice | In vivo were analyzed, showing increased BNZ effect, survival, trypomastigote decrease and lower levels of anti-T-cruzi Ig G 34 dpi. |
| Cevey et al., 2017 | Benznidazole (Antiprotozoal) and Fenofibrate (Antihyperlipidemic) | Balb/c mice | There was a reversal of the cardiac dysfunction associated with the inflammatory response, decreasing pro-inflammatory mediators, with potential for clinical trial in humans. |
| Santeliz et al., 2017 | Dipyridamole (blood Modifier Agent) and nifurtimox (Antiprotozoal) | NMRI albino mice | DPY potentiated the Nfx effect.The association of DPY increased the survival rate to 85%, and all tested parameters were significantly improved. |
| Contreras-Ortiz et al., 2017 | Astaxanthin (antioxidant) and/or nifurtimox (Antiprotozoal) | Vero cells, Balb/c mice | The compound alone did not show any effect on the reduction of parasitemia.Test survival in the acute phase and when associated with NFMX interfered negatively in its activity. |
| Peron et al., 2017 | A3K2A3 (compound of class Dibenzylideneacetone) and benznidazole (Antiprotozoal) or Ketoconazole, or Fluconazole (antifungal) | LLCMK2 cells | The evaluation of the association of A3K2A3 with ketoconazole and benznidazole with greater protection of cells. The association with fluconazole was not effective. |
| Lourenço et al. (2018) | Amiodarone hydrochloride (Antiarrhythmic) and/or Benznidazole (Antiprotozoal) |
T. cruzi (Y strain) cultures with drugs. | Drugs combination was effective, but without synergism, since similar results were obtained when the drugs were tested individually |
| Strauss et al. (2018) | Clomipramine (Antidepressant, tricyclic) Benznidazole (Antiprotozoal) |
Mammalian cells, | Synergistic activity in vitro against the clinically relevant life-stages of T. cruzi. Significantly diminished the parasitic load in blood and the mortality rate |
| Providello et al. (2018) | Ascorbic Acid (Genitourinary Agent) Benznidazole (Antiprotozoal) |
Swiss mice | Reduction in parasitemia, in cardiac parasitism and inflammation, and prevention of the hepatic damage. |
| Scarim et al., 2018b, Scarim et al., 2018a | Hydroxymethylnitrofurazone (a nitrofurazone prodrug) Benznidazole (Antiprotozoal) |
Balb/c mice | Amastigote nests were not found in heart, skeletal muscle, liver, kidney, colon, spleen and brain. The histopathological analysis showed fewer tissue lesions and parasite infiltrates |
| Torrico F et al. (2018) | E1224 (a water-soluble ravuconazole prodrug) | Human | E1224 displayed a transient, suppressive effect on parasite clearance, whereas benznidazole showed early and sustained efficacy until 12 months of follow-up. |
| Guedes-da-Silva et al. (2019) | Sterol 14α-Demethylase (Inhibitor VFV) Benznidazole (Antiprotozoal) |
Swiss Webster mice | parasitemia suppression and 100% animal survival Coadministration of Bz + VFV (resulted in 106-fold lower blood parasitism as compared to the monotherapy of Bz) |
| De Araújo et al. (2019) | Imidazole Derivatives and Benznidazole (Antiprotozoal) | MRC -5 cells and Primary cardiac cells | Potent and selective activity against T. cruzi |
| Rial et al., 2019 | Allopurinol (Antigout) and Benznidazole (Antiprotozoal) | C57BL/6J and C3H/HeN mice | absence of electrical abnormalities, significant reductions in antibody titres and parasitic loads |
| Mazzeti et al., 2019 | Allopurinol combined with benzinidazole (Antiprotozoal) or Nifurtimox (Antiprotozoal) | Mammalian cell, Swiss mice | The interactions were synergic. Administration of the drugs in combination increased the cure rate. |
| Rocha et al. (2019) | Levamisole (anthelminthic) Benznidazole (Antiprotozoal) |
Swiss Webster mice | In vivo: The association partially reduced parasitemia and did not increased animal survival |
ND* not determined.