Abstract: Introduction: Alzheimer’s disesase (AD) is a neurodegenerative disorder characterized by a deterioration of cognitive fuction, memory loss, and behavioral changes. The current pharmacotherapy is limited and focuses only on symptom relief. Therefore, this study aimed to review the targets involved in Alzheimer’s disease (AD) and evaluate the pharmacokinetics and potential interactions of isoeugenol and nine hybrid acetamides derived from it. The pharmacokinetic profiles of the compounds were assessed using ADMET analysis through Deep-PK. For molecular docking, nine hybrid acetamide derivatives of isoeugenol and molecular targets implicated in AD pathophysiology were selected for consensus analysis. All compounds were predicted to exhibit satisfactory pharmacokinetic properties, including good intestinal absorption and blood-brain barrier penetrability. Regarding the toxicological profile, a few derivatives showed potential toxic effects. According to the molecular docking results, the derivatives exhibited satisfactory interactions with five key targets involved in Alzheimer’s disease pathophysiology: apoE4, GABAA, e-NOS, i-NOS, and n-NOS, suggesting potential activity through these pathways. Notably, several compounds showed significant potential activity via the nitric oxide (NO) pathway. The studied compounds demonstrated a favorable pharmacokinetic profile and a high in silico likelihood of modulating Alzheimer’s disease-related pathways, highlighting their potential as candidates for further in vitro and in vivo investigations.
Dias et al. (Sat,) studied this question.