The role of carotenoids from red mamey fruit (Pouteria sapota) against amyloid-β monomers in Alzheimer's disease: Computational analysis and ADMET prediction.

Abstract

Carotenoids, potent antioxidants in fruits and vegetables, have recently garnered attention for their potential therapeutic effects against neurodegenerative diseases. This study focuses on the interaction and anti-aggregation properties of conventional and unconventional carotenoids found in red mamey fruit, a nutraceutical fruit that is a rich source of these compounds. To assess computational the interaction between of amyloid-β (Aβ) peptide with a set of carotenoids and three carotenoids previously explored in experimental assays as well as to assess ADMET prediction of carotenoids selected by computational analysis results. We analyzed the interaction between these carotenoids and Aβ peptides using molecular docking, a key factor in Alzheimer's disease (AD) pathology. Selected carotenoids were compared with the reference compounds cryptocapsin (1), zeaxanthin (2), lutein (3), and cryptocapsin-5,6-epoxide (24), which previously demonstrated significant anti-aggregation activity against Aβ. Using SwissADME and ADMET Predictor® software to determine the pharmaceutical analysis prediction. Computational analysis identified (5R,8R)-sapotexanthin-5,8-epoxide (19) and (5S,8S)-cryptocapsin-5,8-epoxide (26) as the most promising candidates due to their strong binding affinity and potential anti-aggregation properties against Aβ. The pharmaceutical analysis identified compounds (5S,8S)-cryptocapsin-5,8-epoxide (26) and (5R,8R)-cryptocapsin-5,8-epoxide (28) as the most promising compounds. Our findings suggest that specific modifications in the carotenoid structure, particularly modifications in the type of epoxidation and stereochemistry, can significantly influence the biological activity of carotenoids and biopharmaceutical performance. These results provide valuable insights for future in vitro studies of most potential carotenoids (19 and 26) and the development of potential therapeutic agents for AD.