Advances in the discovery of heterocyclic-based drugs against Alzheimer’s disease
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Publication date
2023
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Taylor and Francis
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Sánchez, Juan D, Alcántara, Andrés R, González, Juan F, Sánchez-Montero, José María.Advances in the discovery of heterocyclic-based drugs against Alzheimer’s disease, Expert Opinion on Drug Discovery, Noviembre 2023 18:12, 1413-28, DOI: 10.1080/17460441.2023.2264766
Abstract
Introduction
Alzheimer’s disease is a multifactorial neurodegenerative disorder characterized by beta-amyloid accumulation and tau protein hyperphosphorylation. The disease involves interconnected mechanisms, which can be clustered into two target-packs based on the affected proteins. Pack-1 focuses on beta-amyloid accumulation, oxidative stress, and metal homeostasis dysfunction, and Pack-2 involves tau protein, calcium homeostasis, and neuroinflammation. Against this background heterocyclic system, there is a powerful source of pharmacophores to develop effective small drugs to treat multifactorial diseases like Alzheimer’s.
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This review highlights the most promising heterocyclic systems as potential hit candidates with multi-target capacity for the development of new drugs targeting Alzheimer’s disease. The selection of these heterocyclic systems was based on two crucial factors: their synthetic versatility and their well-documented biological properties of therapeutic potential in neurodegenerative diseases.
Expert opinion
The synthesis of small drugs against Alzheimer’s disease requires a multifactorial approach that targets the key pathological proteins. In this context, the utilization of heterocyclic systems, with well-established synthetic processes and facile functionalization, becomes a crucial element in the design phases. Furthermore, the selection of hit heterocyclic should be guided by a full understanding of their biological activities. Thus, the identification of promising heterocyclic scaffolds with known biological effects increases the potential to develop effective molecules against Alzheimer’s disease.
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Este artículo fue solicitado por encargo al autor sin costes adicionales basado en la experiencia del autor sobre el tema.