Design Strategy and In-Silico Investigation of Indole-Functionalized Isoxazoles as Potential Antiparkinsonism Activity

Abstract

The limitations of currently available antiparkinsonian drugs, including adverse effects and diminished therapeutic efficacy during long term treatment, necessitate the development of novel therapeutic agent with improved safety and effectiveness. In the present study, a series of indole functionalized isoxazole derivatives were rationally designed and investigated through comprehensive insilico approaches as a potential dopamine agonist for the treatment of Parkinson’s disease. Molecular docking studies were performed to evaluate the binding affinity and interaction profiles of the designed derivatives with the dopamine receptor. The docking results demonstrated favourable binding interactions within the receptor active site, with several compounds exhibiting higher binding affinities which compare to the reference dopamine agonist. Drug likeness, physiochemical properties and ADMET profiles were also assessed to predict the pharmacokinetic behaviour and safety of the designed molecules. The integrated computational findings identified the most active derivatives as a promising lead candidate with potential dopamine agonistic activity, providing valuable structural scaffold for thew future development of novel antiparkinsonian agents.