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Erschienen in:

01.06.2013 | Neurology and Preclinical Neurological Studies - Original Article

A therapeutic approach to cerebrovascular diseases based on indole substituted hydrazides and hydrazines able to interact with human vascular adhesion protein-1, monoamine oxidases (A and B), AChE and BuChE

verfasst von: Gerard Esteban, Irene Bolea, Ping Sun, Montse Solé, Abdelouahid Samadi, José Marco-Contelles, Mercedes Unzeta

Erschienen in: Journal of Neural Transmission | Ausgabe 6/2013

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Abstract

Herein, we report the biological evaluation of a series of indole substituted hydrazides and hydrazines throughout the assessment of their multipotent inhibitory potency towards monoamine oxidase (MAO) A and B, semicarbazide-sensitive amine oxidase/vascular adhesion protein-1 (SSAO/VAP-1), and the cholinesterases, acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). Hydrazine JL72 (3-(3-hydrazinylpropyl)-1H-indole) showed a potent, reversible and non-time-dependent inhibition of MAO-A, which suggests its capacity in restoring serotoninergic neurotransmission being devoid of the side effects observed for classic MAO-A inhibitors. In addition, JL72 behaved as a moderate BuChE inhibitor. Finally, both hydrazines and hydrazides derivatives showed high affinity towards SSAO/VAP-1. Among them, JL72 behaved as a noncompetitive and the most potent inhibitor (IC₅₀ = 0.19 ± 0.04 μM), possessing also a significant anti-inflammatory activity. The combined inhibition of SSAO/VAP-1, MAO (A and B), AChE and BuChE appear as an important therapeutic target to be considered in the treatment of cerebrovascular and neurological disorders such as Alzheimer’s disease.

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Titel: A therapeutic approach to cerebrovascular diseases based on indole substituted hydrazides and hydrazines able to interact with human vascular adhesion protein-1, monoamine oxidases (A and B), AChE and BuChE
verfasst von: Gerard Esteban
Irene Bolea
Ping Sun
Montse Solé
Abdelouahid Samadi
José Marco-Contelles
Mercedes Unzeta
Publikationsdatum: 01.06.2013
Verlag: Springer Vienna
Erschienen in: Journal of Neural Transmission / Ausgabe 6/2013
Print ISSN: 0300-9564
Elektronische ISSN: 1435-1463
DOI: https://doi.org/10.1007/s00702-012-0949-x

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