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

被引：32

作者：

Joao Matos, Maria ^{[1
,2
]}

Janeiro, Patricia ^{[1
]}

Gonzalez Franco, Rosa Maria ^{[3
]}

Vilar, Santiago ^{[4
]}

Tatonetti, Nicholas P. ^{[4
]}

Santana, Lourdes ^{[1
]}

Uriarte, Eugenio ^{[1
]}

Borges, Fernanda ^{[2
]}

Angel Fontenla, Jose ^{[5
]}

Vina, Dolores ^{[3
]}

机构：

[1] Univ Santiago de Compostela, Fac Pharm, Dept Organ Chem, Santiago De Compostela 15782, Spain

[2] Univ Porto, Fac Sci, CIQUP Dept Chem & Biochem, P-4100 Oporto, Portugal

[3] Univ Santiago de Compostela, Ctr Res Mol Med & Chron Dis, Dept Pharmacol, Santiago De Compostela 15782, Spain

[4] Columbia Univ, Med Ctr, Dept Biomed Informat, New York, NY 10032 USA

[5] Univ Santiago de Compostela, Fac Pharm, Dept Pharmacol, Santiago De Compostela 15782, Spain

来源：

FUTURE MEDICINAL CHEMISTRY | 2014年 / 6卷 / 04期

关键词：

MAO-B INHIBITORS; AMYLOID PRECURSOR PROTEIN; MONOAMINE-OXIDASE; PARKINSONS-DISEASE; ALZHEIMERS-DISEASE; IN-VITRO; POTENT; ACETYLCHOLINESTERASE; 3-ARYLCOUMARINS; DEMENTIA;

D O I：

10.4155/fmc.14.9

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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 mu 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 Alzheimers disease.

引用

页码：371 / 383

页数：13

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