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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Authors | Gerard Esteban, Irene Bolea, Ping Sun, Montse Solé, Abdelouahid Samadi, José Marco-Contelles, Mercedes Unzeta |
Journal | Journal of neural transmission (Vienna, Austria : 1996)
(J Neural Transm (Vienna))
Vol. 120
Issue 6
Pg. 911-8
(Jun 2013)
ISSN: 1435-1463 [Electronic] Austria |
PMID | 23263540
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Cell Adhesion Molecules
- Hydrazines
- Indoles
- indole
- AOC3 protein, human
- Amine Oxidase (Copper-Containing)
- Monoamine Oxidase
- Acetylcholinesterase
- Butyrylcholinesterase
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Topics |
- Acetylcholinesterase
(metabolism)
- Amine Oxidase (Copper-Containing)
(metabolism)
- Animals
- Butyrylcholinesterase
(drug effects, metabolism)
- Cell Adhesion Molecules
(metabolism)
- Cell Line, Transformed
- Cerebrovascular Disorders
(enzymology, therapy)
- Dose-Response Relationship, Drug
- Drug Interactions
- Humans
- Hydrazines
(chemistry, metabolism)
- Indoles
(chemistry)
- Kinetics
- Leukocytes
(drug effects, metabolism)
- Monoamine Oxidase
(drug effects, metabolism)
- Rats
- Time Factors
- Transfection
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