ISSN print edition: 0366-6352 ISSN electronic edition: 1336-9075 Registr. No.: MK SR 9/7 Published monthly

Identification of potential BACE-1 selective inhibitors against Alzheimer’s disease

Alice C. Barros, Mayra R. do Bomfim, Alex G. Taranto, and Franco H. A. Leite

Universidade Estadual de Feira de Santana, Feira de Santana, Brazil

E-mail: fhenrique@uefs.br

Received: 13 November 2025  Accepted: 21 January 2026

Abstract:

Alzheimer’s disease (AD) is a neurodegenerative disease and principal cause of dementia, affecting more than 55 million people worldwide. The amyloid cascade hypothesis proposes that the β-amyloid peptides, produced by the cleavage of the Amyloid Precursor Protein by BACE-1, are responsible for the onset of the disease. Therefore, BACE-1 has been a target of research and drug design for AD treatment. BACE-1 has a homolog, BACE-2, which is not related to AD and its present and other metabolic pathways. Thus, the design of drugs to treat AD needs to be BACE-1 selective; however, this is not reality for the BACE-1 inhibitors that achieved clinical trials. This work aimed to identify the structural, steric and electronic requirements for the selective inhibition of BACE-1 guided using computational techniques, such as pharmacophore models, molecular docking, molecular dynamic simulations, and free energy calculation. A potential selective BACE-1 inhibitor and selectivity requirements were identified.

Keywords: Alzheimer’s disease; Pharmacophore model; Molecular docking; Molecular dynamics; Free energy calculation

Full paper is available at www.springerlink.com.

DOI: 10.1007/s11696-026-04694-9

Chemical Papers 80 (4) 4323–4339 (2026)