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

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

Research output: Contribution to journalArticleResearchpeer-review

8 Citations (Scopus)

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. © 2012 Springer-Verlag Wien.
Original languageEnglish
Pages (from-to)911-918
JournalJournal of Neural Transmission
Volume120
DOIs
Publication statusPublished - 1 Jun 2013

Keywords

  • Acetylcholinesterase
  • Butyrylcholinesterase
  • Hydrazide
  • Hydrazine
  • Monoamine oxidase
  • Vascular adhesion protein-1

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