Electron affinity, total electronic energy and electron transfer as promising descriptors for estimation of biological activity of thiazolyl-thiadiazines (BACE-1 inhibitors).

Abstract

This paper presents first report on a systematic investigation on developing quantum chemical descriptors on understanding biological activity (pIC₅₀) of a series of 10 thiazolyl-thiadiazines (ID-01 to ID-10) as Beta site amyloid precursor protein cleaving enzyme 1 (BACE-1) protein inhibitors for Alzheimer diseases, under density functional theory. The interactions between inhibitors and model biomolecule are studied in terms of charge and energy transfer, where the target biomolecule at the host BACE-1 protein is identified from the family of 20 amino acids, which are universal to all living organisms. The present study identifies electron affinity (EA), total electronic energy (E), and the electron transfer with amino acid (∆E) of thiazolyl-thiadiazines as promising descriptors, which can explain about 90% of observed biological activity. The developed regression model for training set is also validated for unknown test set of homologous compounds. The developed quantum chemical descriptors for prediction of the biological activity of thiazolyl-thiadiazines will certainly be an excellent addition in the QSAR parlance of drug development.