Synthesis, pharmacological study and docking calculations of new benzo[f]coumarin derivatives as dual inhibitors of enzymatic systems involved in neurodegenerative diseases.

Abstract:

BACKGROUND:Due to the complex etiology of neurodegenerative diseases, there is growing interest in multitarget drugs. In this study we synthesized and evaluated a new series of compounds, with benzo[f]coumarin structure, as potential inhibitors of MAO-A, MAO-B, AChE and BuChE. RESULTS:In vitro studies show that most of the studied compounds inhibited the activity of MAO-B in the nano- to micro-molar range. 3-(3´-methoxyphenyl)benzo[f]coumarin is the most active compound with an IC50 value against MAO-B of 2.44 nM. Most of the derivatives exhibited an important selectivity profile against the MAO-B isoform. Some of them also acted as in vitro inhibitors of BuChE, with 3-(2´-hydroxyphenyl)benzo[f]coumarin being the most active with an IC50 value of 1.13 µM. In addition, a theoretical study of the physicochemical properties of the new compounds, as well as a docking study in both MAO isoforms, were carried out. Important structure-activity relationships were obtained. CONCLUSION:Important preliminary structure-activity relationships were concluded from the experimental results. These results encourage us to further explore the potential of this chemical family as potential drug candidates for the treatment of Alzheimer's disease.

journal_name

Future Med Chem

authors

Matos MJ,Janeiro P,González Franco RM,Vilar S,Tatonetti NP,Santana L,Uriarte E,Borges F,Fontenla JA,Viña D

doi

10.4155/fmc.14.9

subject

Has Abstract

pub_date

2014-03-01 00:00:00

pages

371-83

issue

4

eissn

1756-8919

issn

1756-8927

journal_volume

6

pub_type

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