Anthelmintic activity on Haemonchus contortus and toxicity of benzoyl-carvacrol: a study in vitro, in silico and in vivo.

Abstract

Carvacrol is isolated from essential oils and possesses activity against gastrointestinal nematodes of small ruminants. Benzoylation has been proposed to improve its pharmacological and pharmacokinetic properties. The objectives of this study were to evaluate the ovicidal activity of benzoyl-carvacrol (BC) against Haemonchus contortus, the in silico interaction of BC with the β-tubulin protein and the toxicity of this compound. Carvacrol was subjected to benzoylation and analyzed by gas chromatography coupled to mass spectrometry (GC/MS). The activity of BC and carvacrol was evaluated against H. contortus in the egg hatching test. The in silico study was based on molecular docking with the β-tubulin and thiabendazole used as control. The acute toxicity test was performed with BC and carvacrol by up-and-down procedure (limit test: 2,000 mg/kg) in Wistar rats. GC/MS confirmed the benzoylation. BC and carvacrol inhibited egg hatching by 99.70 and 98.89% at concentrations of 3.16 and 1 mg/mL, respectively, and interacted with β-tubulin. No mortality was caused by compounds, but rats treated with carvacrol demonstrated intoxication signs. These findings indicated that BC showed effect on H. contortus and can potentially interact with β-tubulin of nematodes in addition to presenting toxicological safety in laboratory animals.