In vitro and in silico evaluation of plant compounds as inhibitors of glutathione S-transferase from Rhipicephalus...

Ticks are widely distributed ectoparasites that transmit several pathogens and cause significant losses in livestock production. Resistance to commercial acaricides has become increasingly common, stimulating the search for new molecules with potential for tick control. Among possible targets, glutathione S-transferases (GSTs) play a central role in detoxification processes and are therefore attractive candidates for overcoming acaricide resistance. In this work, the inhibitory activity of plant compounds on recombinant GSTs from Rhipicephalus microplus (rGST-Rm) and R. decoloratus (rGST-Rd) was examined using in vitro and in silico approaches. Compounds tested included 3β-stearioxy-olean-12-ene, diosgenin, quercitrin, naringenin, ellagic acid, rutin, and quercetin, which belong to different chemical classes, including triterpenes, steroids, polyphenols, and flavonoids. In vitro assays showed that 3β-stearioxy-olean-12-ene and naringenin inhibited rGST-Rm with IC₅₀ values of 148.2 μM and 160.7 μM, respectively. For rGST-Rd, inhibition by quercitrin (IC₅₀ = 37.7 μM), naringenin (IC₅₀ = 177.7 μM), and rutin (IC₅₀ = 115.0 μM) was observed. Docking analyses predicted interactions between these molecules and tick GSTs. Overall, the results support the potential of GST inhibition as a strategy for acaricide development and indicate that some plant compounds may serve as starting points for future tick control methods.