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Issue 12, 2015
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Acetophenone derivatives: novel and potent small molecule inhibitors of monoamine oxidase B

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Abstract

Two series of acetophenone derivatives have been designed, synthesized and evaluated for human monoamine oxidase A and B inhibitory activity in vitro. Most of the tested compounds acted preferentially on MAO-B with IC50 values in the nanomolar range and weak or no inhibition of MAO-A. In particular, compounds 1j (IC50 = 12.9 nM) and 2e (IC50 = 11.7 nM) were the most potent MAO-B inhibitors being 2.76- and 2.99-fold more active than selegiline. In addition, the structure–activity relationships for MAO-B inhibition indicated that substituents at C3 and C4 of the acetophenone moiety, particularly with the halogen substituted benzyloxy, were more favorable for MAO-B inhibition. Molecular docking and kinetic studies have been carried out to explain the binding modes of MAO-B with the acetophenone derivatives. Furthermore, the representative compounds 1j and 2e showed low neurotoxicity in SH-SY5Y cells. It may be concluded that the acetophenone derivatives could be used to develop promising lead compounds for treating neurodegenerative diseases.

Graphical abstract: Acetophenone derivatives: novel and potent small molecule inhibitors of monoamine oxidase B

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Article information


Submitted
20 Aug 2015
Accepted
05 Oct 2015
First published
21 Oct 2015

Med. Chem. Commun., 2015,6, 2146-2157
Article type
Concise Article

Acetophenone derivatives: novel and potent small molecule inhibitors of monoamine oxidase B

Z. Wang, X. Li, W. Xu, F. Li, J. Wang, L. Kong and X. Wang, Med. Chem. Commun., 2015, 6, 2146
DOI: 10.1039/C5MD00357A

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