Biological activity of some thiazolyl‐thiadiazines as BACE‐1 inhibitors for Alzheimer's disease in the light of density functional theory based quantum descriptors

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 Al...

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Bibliographic Details
Published in:Journal of physical organic chemistry 2023-12, Vol.36 (12), p.n/a
Main Authors: Mondal Roy, Sutapa, Mehta, Bijal R., Trivedi, Sarthak, Sharma, Bhumika K., Roy, Debesh R.
Format: Article
Language:English
Subjects:
Alzheimer disease
Alzheimer's disease
Amino acids
BACE‐1
Biological activity
Biomolecules
Charge transfer
Density functional theory
Electron affinity
Electron transfer
Energy transfer
Inhibitors
Proteins
QSAR
Quantum chemistry
Regression models
thiazolyl‐thiadiazines
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Summary: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. Electron affinity, total electronic energy and electron transfer as promising descriptors for estimation of biological activity of thiazolyl‐thiadiazines (BACE‐1 inhibitors).
ISSN:0894-3230
1099-1395
DOI:10.1002/poc.4444