QSAR and molecular docking studies on a series of spirocyclic BACE-1 inhibitors
Bashirulla Shaik, Tabassum Zafar, Vijay K. Agrawal, Satya P. Gupta · Journal of Analytical & Pharmaceutical Research · 2022
The most prominent irreversible neurodegenerative disease, Alzheimer’s disease (AD), involves an enzyme, known as β-site APP (amyloid precursor protein) cleaving enzyme?1 (BACE-1). Prediction of potent BACE-1 inhibitors is a potential therapeutic option for the management of AD. The present study deals with the modeling of spirocyclic BACE-1 inhibitors using molecular descriptors to further contribute to better clinical management of AD. A multiple linear regression (MLR) analysis has shown that physicochemical and 2D autocorrelation descriptors of these compounds are the major influencing factors of their activity and a docking study has shown that compounds can form hydrogen bonds with the receptor and have effective steric interactions. The MLR model fits the training set with R2 = 0.857. New potential compounds with higher therapeutic potency than the existing compounds were also docked the enzyme, BACE-1, to validate the formation of hydrogen bonds and hydrophobic interactions. The predicted models will be a constructive approach for the clinical management of Alzheimer’s disease.