Synthesis and biological assessment of racemic benzochromenopyrimidinetriones as promising agents for Alzheimer's disease therapy
| Autor: | Isabel Iriepa, Youssef Dgachi, Fakher Chabchoub, Lhassane Ismaili, José Marco-Contelles, Mourad Chioua, Alexandre Bonet, Hélène Martin, Ignacio Moraleda |
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| Rok vydání: | 2017 |
| Předmět: |
Antioxidant
Stereochemistry Cell Survival medicine.medical_treatment Pharmacology Cholinesterase enzymes 01 natural sciences Heterocyclic Compounds 4 or More Rings Antioxidants 03 medical and health sciences chemistry.chemical_compound Disease therapy Structure-Activity Relationship 0302 clinical medicine Alzheimer Disease Drug Discovery medicine Structure–activity relationship Humans Biological evaluation Cholinesterase ADME Tacrine analogs biology Dose-Response Relationship Drug Molecular Structure 010405 organic chemistry Chemistry Hepatotoxicity Cholinesterase inhibitors Hep G2 Cells medicine.disease Acetylcholinesterase 0104 chemical sciences biology.protein Molecular Medicine Alzheimer's disease Alzheimer’s disease 030217 neurology & neurosurgery Naphthoquinones |
| Zdroj: | Digital.CSIC. Repositorio Institucional del CSIC instname |
| Popis: | Aim: Due to the complex nature of Alzheimer's disease, there is a renewed search for multitarget directed drugs. Results: This paper describes the synthesis and in vitro biological evaluation of six racemic 13-aryl-2,3,4,13-tetrahydro-1H,12H-benzo[6,7]chromeno[2,3-d]pyrido[1,2-a]pyrimidine-7,12,14-triones (1a-6a), and six racemic 15-aryl-8,9,10,11,12,15-hexahydro-14H-benzo[6′,7′]chromeno[2′,3:4,5] pyr-imido [1,2-a]azepine-5,14,16-triones (1b-6b), showing antioxidant and cholinesterase inhibitory capacity. Among these compounds, 13-phenyl-2,3,4,13-tetrahydro-1H,12H-benzo[6,7]chromeno[2,3-d]pyrido[1,2-a]pyrimidine-7,12,14-trione (1a) is a nonhepatotoxic at 300 μmol/l dose concentration, and a selective EeAChE inhibitor showing good antioxidant power. Conclusion: A new family of racemic benzochromenopyrimidinetriones has been investigated for their potential use in the treatment of Alzheimer's disease. |
| Databáze: | OpenAIRE |
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