Synthesis and evaluation of dihydropyrimidinone-derived selenoesters as multi-targeted directed compounds against Alzheimer’s disease
| Autor: | Flavio A. R. Barbosa, Rômulo F. S. Canto, Sumbal Saba, Jamal Rafique, Antonio L. Braga |
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| Rok vydání: | 2016 |
| Předmět: |
Drug
Antioxidant media_common.quotation_subject medicine.medical_treatment Clinical Biochemistry Pharmaceutical Science Pyrimidinones 010402 general chemistry 01 natural sciences Biochemistry Antioxidants Lipid peroxidation Structure-Activity Relationship chemistry.chemical_compound Alzheimer Disease Organoselenium Compounds Drug Discovery Galantamine medicine TBARS Humans Structure–activity relationship Molecular Biology media_common Cholinesterase Dose-Response Relationship Drug Molecular Structure biology 010405 organic chemistry Organic Chemistry Esters Acetylcholinesterase 0104 chemical sciences chemistry biology.protein Molecular Medicine Cholinesterase Inhibitors medicine.drug |
| Zdroj: | Bioorganic & Medicinal Chemistry. 24:5762-5770 |
| ISSN: | 0968-0896 |
| Popis: | This paper describes the synthesis and evaluation of new dihydropyrimidinone (DHPM)-derived selenoesters as potential multi-targeted agents for the treatment of Alzheimer's disease. A series of DHPM-derived selenoesters were obtained with high structural diversity through a short and modular synthetic route. The antioxidant activity was evaluated by TBARS and iron chelation assays. These compounds were also evaluated as acetylcholinesterase inhibitors (AChEi). The compounds demonstrated good antioxidant activity, since they presented excellent lipid peroxidation inhibition and good iron chelation activity. In addition, they showed acetylcholinesterase inhibition activity and some of them presented activity superior to that of the standard drug galantamine. The in silico predictions showed that the compound 1h may present a good pharmacokinetic profile. Therefore, the series of DHPM-derived selenoesters described herein displayed good potential for the development of antioxidant and anticholinesterasic agents in the search for new multi-targeted therapeutics for the treatment of Alzheimer's disease. (C) 2016 Elsevier Ltd. All rights reserved. |
| Databáze: | OpenAIRE |
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