Arthur Lins Dias, Pablo Rayff da Silva, Hugo Fernandes Oliveira Pires, Livia Roberta Pimenta Souza, Natália Ferreira de Sousa, Alan Ferreira Alves, Jéssica Cabral de Andrade, Luiza Cristine Diniz Neri, Maria Clara Ferreira Goncalves, Cícero Francisco Bezerra Felipe, Mirian Graciela da Silva Stiebbe Salvadori, Marcus T Scotti, Luciana Scotti
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引用次数: 0
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.
期刊介绍：
Current Topics in Medicinal Chemistry is a forum for the review of areas of keen and topical interest to medicinal chemists and others in the allied disciplines. Each issue is solely devoted to a specific topic, containing six to nine reviews, which provide the reader a comprehensive survey of that area. A Guest Editor who is an expert in the topic under review, will assemble each issue. The scope of Current Topics in Medicinal Chemistry will cover all areas of medicinal chemistry, including current developments in rational drug design, synthetic chemistry, bioorganic chemistry, high-throughput screening, combinatorial chemistry, compound diversity measurements, drug absorption, drug distribution, metabolism, new and emerging drug targets, natural products, pharmacogenomics, and structure-activity relationships. Medicinal chemistry is a rapidly maturing discipline. The study of how structure and function are related is absolutely essential to understanding the molecular basis of life. Current Topics in Medicinal Chemistry aims to contribute to the growth of scientific knowledge and insight, and facilitate the discovery and development of new therapeutic agents to treat debilitating human disorders. The journal is essential for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important advances.
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