Virtual screening, molecular docking simulation and ADMET prediction of some selected natural products as potential inhibitors of NLRP3 inflammasomes as drug candidates for Alzheimer disease

Abstract

Alzheimer's disease (AD) is a disorder affecting brain cells, resulting in brain neuron death. AD is most commonly diagnosed in people over the age of 65, with symptoms of memory loss and cognitive dysfunction. Natural bioactive products have been established to be effective for the prevention and treatment of patients with multiple and complex health conditions, including neurodegenerative disorders. These compounds are among the most favorable source of drug candidates, a more rational and economic search for new lead structures from nature and must therefore be a priority in order to overcome health challenges like AD and several others. Researchers have shown a strong interest in the design and fabrication of novel therapeutics based on naturally isolated molecules in recent years. These factors necessitated the use of Docking Molecular Simulations, Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) predictions in the design and synthesis of new drug for the treatment of AD. In comparison to the reference drug, sixteen of the twenty-two natural products (NP) used had lower, better binding energies and excellent good pose interactions. Docking interactions revealed that the chosen NP fits well into the NOD-Like Receptor Pyrin Domain-Containing 3 (NLRP3) protein's ATP-binding site, forming a bond with some of the protein. Furthermore, the ADMET predictions indicate that six compounds penetrated the blood brain barrier (BBB), demonstrating their potential. As a result, these compounds with brilliant and excellent predictive potentials can be tested further as drug candidates in the treatment of AD. Our findings revealed that NP is an active NLRP3 inflammasome inhibitor and offer new confirmation for its use as an AD treatment agent.