IMIDAZOLIDINEDIONE AND STRUCTURALLY RELATED COMPOUNDS AS POSSIBLE HUMAN MAO-B INHIBITORS FOR PARKINSON’S DISEASE: AN IN-SILICO ASSESSMENT

The study described here is based on an in-silico approach to rank seven thiazolo-imidazoles and similar compounds, selected using Chem-mimic and PubChem similarity indices, for Parkinson’s disease bioactivity, with the receptor target PDB ID 2V5Z. An AI-based approach using DiffDock-L and Alfa Flow NeuroSnap AI was used for docking and dynamic simulation studies. Sprint-AI was used for ranking and bioactivity assessment. The physical disabilities associated with Parkinson’s disease include paucity of movement, muscle stiffness, and tremor at rest. It is a progressive neurodegeneration of the substantia nigra with neuronal loss in the pars compacta. Levodopa was used to treat Parkinson’s disease. This resulted in improved memory, temporary sleeplessness, and a feeling of heaviness. Anticholinergics were used before Levodopa. A monoamine oxidase inhibitor was used to increase dopamine levels. Imidazole scaffolds, with or without a sulfur atom in the ring system, proved useful for PD treatment. Imidazoles possess neuroprotective activity that reduces neuroinflammation associated with PD. They inhibit PDE10A, which is associated with PD neuroinflammation. The sulfur atom helps with BBB penetration. Prediction: AI-ADMET from NeuroSnap performed the pharmacokinetic prediction. Most of the compounds complied with the Lipinski Rule of 5 and met toxicity parameters. The best predicted activity was observed for 3-amino-5,5-diphenyleimidazole-2,5-diene. The reference compound for redocking was Sufanimide (-8.73). Further lead optimization and clinical studies are required to develop analogs of this hit compound.