Synthesis, <i>in silico</i> screening and anthelmintic activity of chlorine containing chalcones

Objectives: Chalcones, which are precursors to flavonoids, consist of two aromatic rings linked by a three-carbon unsaturated carbonyl system and are known for a variety of biological activities, including antibacterial and anticancer properties. They are typically synthesized via Claisen–Schmidt condensation. Given the global burden of helminth infections, particularly in regions with poor sanitation, this study aimed to synthesize chalcone derivatives and evaluate their anthelmintic potential through in vitro testing and in silico molecular docking approaches. Material and Methods: Chalcones were synthesized by combining substituted benzaldehydes with p -chloroacetophenone. Thin-layer chromatography was used to monitor the reaction, and chloroform was used to recrystallize the final products. Molecular docking studies using Molegro Virtual Docker analyzed binding interactions between the chalcones and proteins. In vitro anthelmintic activity was tested on Eisenia fetida earthworms, using albendazole as a reference. Test solutions (1.25 mg/mL and 2.50 mg/mL) were prepared in dimethyl formamide, and paralysis and death times of the worms were recorded. All experiments were conducted in triplicate for consistency. Results: The study employed Molegro Virtual Docker to forecast interactions between tubulin-colchicine and manufactured chalcones. Docking scores for most drugs were comparable to those of the reference standard, albendazole, indicating a strong binding affinity. Compound 2 (−115.442) and 4 (−115.086) showed the highest binding affinities, and four compounds were chosen for synthesis based on binding affinity and reaction feasibility. According to in vitro studies, compounds 1–4 had more potent anthelmintic activity against E. fetida than albendazole. Comparing the compounds to albendazole, the worms were paralyzed and killed more quickly. When it comes for treating helminthic infections, the chalcones have displayed promising effects. Conclusion: The study synthesized chlorine-containing chalcones that showed greater effectiveness than albendazole against helminths in E. fetida tests. Strong binding to tubulin-colchicine was revealed by in silico investigations. Subsequent research will concentrate on toxicity assessments and more extensive helminthic infection testing.