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

• Type: Article in International Scientific Journal
• Date: 2014

Authors

matos, mj (Author) Other; janeiro, p (Author) Other; gonzalez franco, rm (Author) Other; vilar, s (Author) Other; tatonetti, np (Author) Other; santana, l (Author) Other; uriarte, e (Author) Other; borges, f (Author) FCUP; fontenla, ja (Author) Other; vina, d (Author) Other

Journal

Title: Future Medicinal Chemistry

Vol. 6

Pages: 371-383

ISSN: 1756-8919

Publisher: Future Medicine Ltd.

Indexing

ISI Web of Knowledge - 30 Citations

Scopus - 30 Citations

Other information

Authenticus ID: P-009-9RG

DOI: 10.4155/fmc.14.9

Abstract (EN): 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 IC 50 value of 1.13 ̄M. 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. © 2014 Future Science Ltd.

Language: English

Type (Professor's evaluation): Scientific