Exploration of new scaffolds as potential MAO-A inhibitors using pharmacophore and 3D-QSAR based in silico screening
| Autor: | Mugdha R. Suryawanshi, Kakasaheb R. Mahadik, Radha Charan Dash, Sharad H. Bhosale, Suhas M. Shelke |
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| Rok vydání: | 2010 |
| Předmět: |
Virtual screening
Quantitative structure–activity relationship Binding Sites Monoamine Oxidase Inhibitors Molecular model Databases Factual Chemistry Stereochemistry In silico Organic Chemistry Clinical Biochemistry Pharmaceutical Science Quantitative Structure-Activity Relationship MAO-A Inhibitors Biochemistry Fitness score Docking (molecular) Catalytic Domain Drug Discovery Molecular Medicine Computer Simulation Pharmacophore Molecular Biology Monoamine Oxidase |
| Zdroj: | Bioorganicmedicinal chemistry letters. 21(8) |
| ISSN: | 1464-3405 |
| Popis: | Monoamine oxidase-A (MAO-A) inhibitors are of particular importance in the treatment of depressive disorders. Herein described is pharmacophore generation and atom-based 3D-QSAR analysis of previously reported pyrrole based MAO-A inhibitors in order to get insight into their structural requirements responsible for high affinity. The best pharmacophore model generated consisted of four features DHHR: a hydrogen bond donor (D), two hydrophobic groups (H) and an aromatic ring (R). Based on model generated, a statistically valid 3D-QSAR with good predictability was developed. Derived pharmacophore was used as a query to search Zinc 'clean drug-like' database. Hits retrieved were passed progressively through filters like fitness score, predicted activity and docking scores. The survived hits present new scaffolds with a potential for MAO-A inhibition. |
| Databáze: | OpenAIRE |
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