Avaliação da ação anti-helmíntica in vitro de 2-aril-3-(2- morfolinoetil)tiazolidin-4-onas e de 2-aril-3-(3-morfolinopropil)tiazolidin-4- onas contra ovos de Fasciola hepatica (Linnaeus, 1758)

Abstract

Derivatives thiazolidin-4-onas are heterocyclic compounds which have shown different biological activities. However, there are no reports of studies with anthelmintic activity, in particular against the trematode Fasciola hepatica (F. hepatica). This helminth is the etiologic agent of fascioliasis, a disease that affects humans and animals, causing damage to the liver and bile duct. The treatment takes place by using fasciolicidas drugs such as, for example, triclabendazole and other benzimidazoles, of which already shows this parasite resistance and studies for the development of new drugs are scarce fasciolicidas. Therefore the objective of this study was to evaluate the action ovicida through eggs hatch assay (EHA) of two systematic series of derivatives of thiazolidin-4-ones (2-aryl-3-(2- morpholinoethyl)thiazolidin-4-ones (1a-h) and 2-aryl-3-(2-morpholinopropyl) thiazolidin-4-ones) (2a-h) on F. hepatica eggs. The EHA were performed in triplicate and accompanied by a negative control (distilled water and the suspension egg), positive control (Thiabendazole 25μg/mL and the suspension eggs) and control dimethylsulfoxide solvent (DMSO) in the concentration of 0.5 % and the suspension eggs. The Compounds were diluted in DMSO in order to obtain final concentrations of 0.002 μg/mL, 0.02 μg/mL, 0.2 μg/mL, 2 μg/mL e 20 μg/mL. The cytotoxicity assay evaluated the metabolic function by mitochondrial dehydrogenase activity bovine kidney cells (MDBK) using 3- (4,5-dimethylthiazol- 2-yl) -2,5-diphenyltetrazolium bromide (MTT) to indicate the viability cell. It was observed that the 1a-h compounds presented no reduction in hatching ratio of eggs compared to the negative control group. The series of compounds 2a-h show effective reduction (p <0.001) in the ratio of hatching eggs. Compound 2b (aryl = C6H4-2,4-F) showed an efficacy of 96% at the highest concentration (20 μg/ml) and a cell viability of 96%. Compound 2e (aryl = C6H4-4-Cl) showed efficacy against F. hepatica eggs in all tested concentrations and the higher cell viability (92%) occurred at low concentrations (0.02 μg/ml to 0.002 μg/ml). According to the results, it can be stated that the compounds 1a-h show no ovicidal activity against F. hepatica eggs, and compounds 2a-h, in particular the compounds 2b and 2e inhibit hatching of eggs F . hepatica and could be a promising alternative for the control of fascioliasis.