Synthesis and in vitro evaluation of pteridine analogues as monoamine oxidase B and nitric oxide synthase inhibitors
| Autor: | Sarel F. Malan, Louis H.A. Prins, Jacobus P. Petzer |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Monoamine Oxidase Inhibitors
Stereochemistry Clinical Biochemistry Molecular Conformation Pharmaceutical Science Crystallography X-Ray Biochemistry Chemical synthesis Catalytic Domain Drug Discovery medicine Animals Humans Computer Simulation Enzyme Inhibitors Molecular Biology Monoamine Oxidase chemistry.chemical_classification Binding Sites biology Bicyclic molecule Pteridines Organic Chemistry Neurodegenerative Diseases In vitro Nitric oxide synthase Enzyme Neuroprotective Agents chemistry Enzyme inhibitor Drug Design biology.protein Molecular Medicine Monoamine oxidase B Nitric Oxide Synthase Pteridine medicine.drug Papio |
| Zdroj: | Bioorganicmedicinal chemistry. 17(21) |
| ISSN: | 1464-3391 |
| Popis: | Monoamine oxidase B (MAO-B) and nitric oxide synthase (NOS) have both been implicated in the pathology of neurodegenerative diseases. In an attempt to design dual-target-directed drugs that inhibit both these enzymes, a series of pteridine-2,4-dione analogues were synthesised. The compounds were found to be relatively weak NOS inhibitors but showed promising MAO-B activity with 6-amino-5-[( E )-3-(3-chloro-phenyl)-prop-2-en-( E )-ylideneamino]-1,3-dimethyl-1 H -pyrimidine-2,4-dione and 6-[( E )-2-(3-chloro-phenyl)-vinyl]-1,3-dimethyl-1 H -pteridine-2,4-dione inhibiting MAO-B with IC 50 values of 0.602 and 0.314 μM, respectively. The pteridine-2,4-dione analogues thus show promise as scaffolds for the development of potent reversible MAO-B inhibitors and as observed in earlier studies, the most potent inhibitors were obtained with 3-chlorostyryl substitution. |
| Databáze: | OpenAIRE |
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