Toxocara canis: avaliação in vitro, in silico e ex vivo de moléculas sintéticas derivadas da cumarina

Abstract

Human toxocariasis is a neglected tissue parasitosis, whose main etiological agent is the nematode Toxocara canis. Benzomidazole, anthelmintics of choice for this parasitosis treatment, have clinical resolution rates between 45 and 70%, due to its low water solubility and difficult action at the tissue level. The objective of this study was evaluate in vitro the activity of synthetic molecules derived from coumarin (COU), on Toxocara canis larvae, in addition to evaluating these molecules in silico and ex vivo. Eleven molecules were evaluated (1 mg/mL), in duplicate, in microculture plates containing T.canis larvae in RPMI -1640 medium, being incubated at 37°C, in 5% CO2 tension, for 48 hours. After, it was determined the minimum larvicidal concentration (CLM). The COU 9 molecule, at 1 mg/mL CLM, and the COU 6 molecule, at 0,5 mg/mL CLM, obtained results against 100% of T.canis larvae. The in silico analyses of COU 6 and COU 9 molecules were used the softwares: Swiss ADME and Molinspiration. The molecules showed high metabolism capacity and gastrointestinal absorption, besides having the ability to permeate the blood brain barrier. Another important result, was the absence of cytotoxicity of the COU 9 molecule at the effective CLM (1 mg/mL). Under the conditions studied, it is concluded that COU 9 molecule is candidate for prototype compound and pre-clinical testing, and the COU 6 molecule is a potential candidate.