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cis-cyclopropylamines as mechanism-based inhibitors of monoamine oxidases

Malcomson, Thomas, Yelekci, Kemal, Borrello, Maria Teresa and Arasu, Ganesan (2015) cis-cyclopropylamines as mechanism-based inhibitors of monoamine oxidases. The FEBS Journal, 282 (16). pp. 3190-3198. ISSN 1742-464X (In Press)

Item Type: Article


Cyclopropylamines, inhibitors of monoamine oxidases (MAO) and lysine�specific demethylase (LSD1), provide a useful structural scaffold for the
design of mechanism-based inhibitors for treatment of depression and can�cer. For new compounds with the less common cis relationship and with an
alkoxy substituent at the 2-position of the cyclopropyl ring, the apparent
affinity determined from docking experiments revealed little difference
between the enantiomers. Using the racemate, kinetic parameters for the
reversible and irreversible inhibition of MAO were determined. No inhibition
of LSD1 was observed. For reversible inhibition, most compounds gave high
IC50 values with MAO A, but sub-micromolar values with MAO B. After
pre-incubation of the cyclopropylamine with the enzyme, the inhibition was
irreversible for both MAO A and MAO B, and the activity was not restored
by dilution. Spectral changes during inactivation of MAO A included
bleaching at 456 nm and an increased absorbance at 400 nm, consistent with
flavin modification. These derivatives are MAO B-selective irreversible inhib�itors that do not show inhibition of LSD1. The best inhibitor was cis-N-ben�zyl-2-methoxycyclopropylamine, with an IC50 of 5 nM for MAO B and
170 nM for MAO A after 30 min pre-incubation. This cis-cyclopropylamine
is over 20-fold more effective than tranylcypromine, so may be studied as a
lead for selective inhibitors of MAO B that do not inhibit LSD1.

The FEBS Journal - 2015 - Malcomson - cis‐cyclopropylamines as mechanism‐based inhibitors of monoamine oxidases.pdf - Published Version

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Depositing User: Teresa Borrello


Item ID: 17442
Identification Number:
ISSN: 1742-464X
Official URL:

Users with ORCIDS

ORCID for Maria Teresa Borrello: ORCID iD

Catalogue record

Date Deposited: 18 Mar 2024 13:26
Last Modified: 18 Mar 2024 13:30


Author: Maria Teresa Borrello ORCID iD
Author: Thomas Malcomson
Author: Kemal Yelekci
Author: Ganesan Arasu

University Divisions

Faculty of Health Sciences and Wellbeing > School of Pharmacy and Pharmaceutical Sciences


Sciences > Chemistry
Sciences > Pharmacy and Pharmacology

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