Etersalate prevents the formations of 6Aβ16-22 oligomer: An in silico study

Abstract

Oligomerization of amyloid beta (Aβ) peptides has been considered as the crucially causative agent in the development of Alzheimer’s disease. Etersalate, a nonsteroidal anti-inflammatory oral drug (United State Food and Drug Administration—Unique Ingredient Identifier: 653GN04T2G) was previously suggested to bind well to proto-fibrils of Aβ peptides in silico. Here, the effect of etersalate on the oligomerization of soluble Aβ16–22 hexamer (6Aβ16–22) were extensively investigated using temperature replica exchange molecular dynamics (REMD) simulations over ~16.8 μs in total for 48 replicas (350 ns per replica). The results reveal that etersalate can enter the inner space or bind on the surface of 6Aβ16–22 conformations, which destabilizes the hexamer. Etersalate was predicted to able to cross the blood brain barrier using prediction of absorption, distribution, metabolism, and excretion—toxicity (preADMET) tools. Overall, although the investigation was performed with the low concentration of trial inhibitor, the obtained results indicate that etersalate is a potential drug candidate for AD through inhibiting formation of Aβ oligomers with the average binding free energy of -11.7 kcal/mol.