Drug Res (Stuttg) 2018; 68(12): 687-695
DOI: 10.1055/a-0620-8309
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

Synthesis and in vitro Evaluation of 2-heteroarylidene-1-tetralone Derivatives as Monoamine Oxidase Inhibitors

Klaudia T. Amakali
1   Centre of Excellence for Pharmaceutical Sciences, North-West University, Potchefstroom, South Africa
,
Lesetja J. Legoabe
1   Centre of Excellence for Pharmaceutical Sciences, North-West University, Potchefstroom, South Africa
,
Anél Petzer
1   Centre of Excellence for Pharmaceutical Sciences, North-West University, Potchefstroom, South Africa
2   Pharmaceutical Chemistry, School of Pharmacy, North-West University, Potchefstroom, South Africa
,
Jacobus P. Petzer
1   Centre of Excellence for Pharmaceutical Sciences, North-West University, Potchefstroom, South Africa
2   Pharmaceutical Chemistry, School of Pharmacy, North-West University, Potchefstroom, South Africa
› Author Affiliations
Further Information

Publication History

received 14 March 2018

accepted 19 April 2018

Publication Date:
14 May 2018 (online)

Abstract

The present study investigates the human monoamine oxidase (MAO) inhibition properties of a series of twelve 2-heteroarylidene-1-tetralone derivatives. Also included are related cyclohexylmethylidene, cyclopentylmethylidene and benzylidene substituted 1-tetralones. These compounds are related to the 2-benzylidene-1-indanone class of compounds which has previously been shown to inhibit the MAOs, with specificity for the MAO-B isoform. The target compounds were synthesised by the Claisen-Schmidt condensation between 7-methoxy-1-tetralone or 1-tetralone, and various aldehydes, under acid (hydrochloric acid) or base (potassium hydroxide) catalysis. The results of the MAO inhibition studies showed that the 2-heteroarylidene-1-tetralone and related derivatives are in most instances more selective inhibitors of the MAO-B isoform compared to MAO-A. (2E)-2-Benzylidene-7-methoxy-3,4-dihydronaphthalen-1(2 H)-one (IC50=0.707 μM) was found to be the most potent MAO-B inhibitor, while the most potent MAO-A inhibitor was (2E)-2-[(2-chloropyridin-3-yl)methylidene]-7-methoxy-3,4-dihydronaphthalen-1(2 H)-one (IC50=1.37 μM). The effect of the heteroaromatic substituent on MAO-B inhibition activity, in decreasing order was found to be: cyclohexyl, phenyl>thiophene>pyridine, furane, pyrrole, cyclopentyl. This study concludes that, although some 2-heteroarylidene-1-tetralone derivatives are good potency MAO inhibitors, in general their inhibition potencies, particularly for MAO-B, are lower than structurally related chalcones and 1-indanone derivatives that were previously studied.

 
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