Prediction on the anthelmintic effects of some herbal ligands and their derivatives with in silico molecular modelling method

Helminthic infections are quite common around the world and more than 2 billion people are infected with at least one helminth species. In this study, it was aimed to model a new anthelmintic drug candidate, which can act at lower doses than the most commonly used anthelmintic drugs in the market, with less side effects, easy to access and reliable, using herbal ligand scaffolds, and to show the anthelmintic effect of some plant extracts on pinworms. Since development of resistance requires the discovery of new anthelmintics, the most potent herbal ligands were investigated via docking simulations to inhibit mutant proteins that may arise in the event of anthelmintic resistance development. Eriocitrin was used as a scaffold for drawing derivatives. The secondary structures of some target proteins were predicted by homology modeling because their 3D structures are unknown. As a result, in this study, it was revealed for the first time that cucurbitacin-B can inhibit rat carnitine palmitoyl transferase 2 enzyme with an exceptionally good score value (Ki= 57,11 picomolar and ΔG=-13,97 kcal/mol), and arteannuin-B is a more potent drug candidate than Mebendazole in the development of resistance. Among the 24 designed eriocitrin derivatives, E05 has a lower Ki value than eriocitrin, oreganol is a selective inhibitor candidate and the selectivity index for fumarate reductase is 20 310,53, and in vivo experiments, Artemisia annua L. n-hexane extract was an antinematodal effect of 36,91% at the 1200 mg/kg dose against pinworms.