MAO Inhibitory Activity of 2‐Arylbenzofurans versus 3‐Arylcoumarins: Synthesis,in vitro Study,and Docking Calculations |
| |
Authors: | Dr. Giulio Ferino Prof. Enzo Cadoni Dr. Maria João Matos Dr. Elias Quezada Prof. Eugenio Uriarte Prof. Lourdes Santana Dr. Santiago Vilar Dr. Nicholas P. Tatonetti Matilde Yáñez Dolores Viña Dr. Carmen Picciau Dr. Silvia Serra Prof. Giovanna Delogu |
| |
Affiliation: | 1. Department of Chemical and Geological Sciences, University of Cagiari, S.S. 554, 09042 Monserrato Cagliari (Italy);2. Department of Organic Chemistry, Faculty of Pharmacy, University of Santiago de Compostela, 15782 Santiago de Compostela (Spain);3. Department of Biomedical Informatics, Columbia University Medical Center, New York, NY 10032 (USA);4. Department of Pharmacology, CIMUS, University of Santiago de Compostela, 15782 Santiago de Compostela (Spain);5. Department of Life Sciences and Environment, Section of Pharmaceutical Sciences, University of Cagliari, 09124 Cagliari (Italy) |
| |
Abstract: | Monoamine oxidase (MAO) is an important drug target for the treatment of neurological disorders. Several 3‐arylcoumarin derivatives were previously described as interesting selective MAO‐B inhibitors. Preserving the trans‐stilbene structure, a series of 2‐arylbenzofuran and corresponding 3‐arylcoumarin derivatives were synthesized and evaluated as inhibitors of both MAO isoforms, MAO‐A and MAO‐B. In general, both types of derivatives were found to be selective MAO‐B inhibitors, with IC50 values in the nano‐ to micromolar range. 5‐Nitro‐2‐(4‐methoxyphenyl)benzofuran ( 8 ) is the most active compound of the benzofuran series, presenting MAO‐B selectivity and reversible inhibition (IC50=140 nM ). 3‐(4′‐Methoxyphenyl)‐6‐nitrocoumarin ( 15 ), with the same substitution pattern as that of compound 8 , was found to be the most active MAO‐B inhibitor of the coumarin series (IC50=3 nM ). However, 3‐phenylcoumarin 14 showed activity in the same range (IC50=6 nM ), is reversible, and also severalfold more selective than compound 15 . Docking experiments for the most active compounds into the MAO‐B and MAO‐A binding pockets highlighted different interactions between the derivative classes (2‐arylbenzofurans and 3‐arylcoumarins), and provided new information about the enzyme–inhibitor interaction and the potential therapeutic application of these scaffolds. |
| |
Keywords: | 2‐arylbenzofurans 3‐arylcoumarins docking inhibitors monoamine oxidase reversibility |
|
|