Title:From Hybrids to New Scaffolds: The Latest Medicinal Chemistry Goals in Multi-target Directed Ligands for Alzheimer’s Disease
Volume: 19
Issue: 6
Author(s): Jazmín Alarcón-Espósito*, Michael Mallea and Julio Rodríguez-Lavado*
Affiliation:
- Departamento de Quimica Organica y Fisicoquimica, Facultad de Ciencias Quimicas y Farmaceuticas, Universidad de Chile, Olivos 1007, Independencia, Santiago,Chile
- Departamento de Quimica Organica y Fisicoquimica, Facultad de Ciencias Quimicas y Farmaceuticas, Universidad de Chile, Olivos 1007, Independencia, Santiago,Chile
Keywords:
Alzheimer disease, multi-target directed ligands, cholinesterase inhibitors, serotonin transporter, 5-HT receptors,
β – amyloid aggregation, tau protein, monoamine oxidase.
Abstract: Alzheimer’s disease (AD) is a chronic, progressive, and fatal neurodegenerative disorder
affecting cognition, behavior, and function, being one of the most common causes of mental deterioration
in elderly people. Once thought as being just developed because of β amyloid depositions
or neurofibrillary Tau tangles, during the last decades, numerous AD-related targets have
been established, the multifactorial nature of AD became evident. In this context, the one drug-one
target paradigm has resulted in being inefficient in facing AD and other disorders with complex etiology,
opening the field for the emergence of the multitarget approach. In this review, we highlight
the recent advances within this area, emphasizing in hybridization tools of well-known chemical
scaffolds endowed with pharmacological properties concerning AD, such as curcumin-, resveratrol-,
chromone- and indole-. We focus mainly on well established and incipient AD therapeutic targets,
AChE, BuChE, MAOs, β-amyloid deposition, 5-HT4 and Serotonin transporter, with the aim
to shed light about new insights in the AD multitarget therapy.
