Natural compounds with potential acaricidal activity against Rhipicephalus microplus: molecular docking screening of glutathione S-transferase inhibitors

The cattle tick Rhipicephalus microplus is one of the most important ectoparasites affecting livestock worldwide, causing substantial economic losses through reduced animal productivity, pathogen transmission, and the costs associated with chemical control. The intensive use of acaricides has contributed to the emergence of resistant tick populations and environmental contamination, underscoring the need for innovative, sustainable control strategies aligned with the One Health approach. In this context, glutathione S-transferase (GST), an enzyme involved in detoxification and acaricide resistance, has emerged as a promising molecular target for developing new acaricidal compounds. Therefore, this study aimed to identify natural compounds with potential inhibitory activity against GST of R. microplus using molecular docking approaches. The three-dimensional structure of GST from R. microplus was obtained from the AlphaFold Protein Structure Database. A total of 1,000 natural compounds were retrieved from the Natural Products Atlas. Molecular docking simulations were performed at the GST H-site using Molegro Virtual Docker. Compounds were ranked according to MolDock Score values, and the best docking poses were further evaluated for intermolecular interactions and ADMET properties. The ten best-ranked compounds showed MolDock Scores ranging from −156.264 to −137.364. Several compounds exhibited favorable predicted pharmacokinetic profiles, including high intestinal absorption and absence of AMES toxicity or skin sensitization. Notably, none of the ten top-ranked compounds has previously been reported as a GST inhibitor of R. microplus or evaluated for acaricidal activity against this tick species. These findings identify novel natural compounds with predicted affinity for GST and highlight their potential as candidates for future in vitro and in vivo studies. By supporting the development of acaricidal agents with innovative mechanisms of action, these compounds may contribute to reducing reliance on conventional acaricides, mitigating environmental contamination, slowing the selection of resistant tick populations, and promoting more sustainable livestock production.