Title:Recent Highlights on Molecular Hybrids Potentially Useful in Central Nervous System Disorders
Volume: 17
Issue: 6
Author(s): Mariana Matias, Samuel Silvestre, Amílcar Falcao and Gilberto Alves
Affiliation:
Keywords:
Alzheimer's disease, central nervous system, epilepsy, molecular hybridization, pain, Parkinson's disease.
Abstract: Molecular hybridization is a recent strategy based on the covalent fusion of two or more
pharmacophores to create a single molecule with multiple mechanisms of action, which represents an
encouraging approach in the development of new drugs with potential therapeutic application in several
pathologies. This review provides a comprehensive perspective of the most relevant advances in the
development of hybrid molecules acting in the central nervous system. For instance, several opioid
hybrids based on endogenous opioid peptides (e.g. enkephalins, deltorphins and endomorphins) have
been developed, and γ-aminobutyric acid agonists have also been designed for neuropathic pain control.
In addition, a number of hybrid compounds have also been synthesized and evaluated for their
anticonvulsant activity and neurotoxicity, which may be further developed as potential antiepileptic
drugs. Moreover, several hybrid compounds have also been designed for the treatment of
neurodegenerative diseases focusing primarily on Alzheimer’s disease by targeting the cholinergic
neurotransmission, as acetylcholinesterase inhibitors, and the amyloid β-protein deposition. There are
also studies addressing hybrid compounds including an antioxidant moiety, which can be potentially
useful in Alzheimer’s and Parkinson’s diseases and other neurodegenerative disorders. Additionally,
other research works have also shown promising hybrid molecules for depression, autism and cocaine
addiction. Thus, the development of molecular hybrid compounds seems to be a promising strategy in
the discovery of novel therapeutic drugs.
