Detalle de: Functionalized aromatic esters of the Amaryllidaceae alkaloid haemanthamine and their in vitro and in silico biological activity connected to Alzheimer’s disease
| Title | Functionalized aromatic esters of the Amaryllidaceae alkaloid haemanthamine and their in vitro and in silico biological activity connected to Alzheimer’s disease |
| Abstract |
A novel series of aromatic esters (1a-1m) related to the Amaryllidaceae alkaloid (AA) haemanthamine were designed, synthesized and tested in vitro with particular emphasis on the treatment of neurodegenerative diseases. Some of the synthesized compounds revealed promising acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitory profile. Significant human AChE (hAChE) inhibition was demonstrated by 11-O-(3-nitrobenzoyl)haemanthamine (1j) with IC 50 value of 4.0 ± 0.3 µM. The strongest human BuChE (hBuChE) inhibition generated 1-O-(2-methoxybenzoyl)haemanthamine (1g) with IC 50 value 3.3 ± 0.4 µM. Moreover, 11-O-(2-chlorbenzoyl)haemanthamine (1m) was able to inhibit both enzymes in dose-dependent manner. The mode of hAChE and hBuChE inhibition was minutely inspected using enzyme kinetic analysis in tandem with in silico experiments, the latter elucidating crucial interaction in 1j-, 1m-hAChE and 1g-, 1m-hBuChE complexes. The blood-brain barrier (BBB) permeability was investigated applying the parallel artificial membrane permeation assay (PAMPA) to predict the CNS availability of the compounds. |
| Apa Reference | Peřinová, R., Maafi, N., Korábečný, J., Kohelová, E., De Simone, A., Al Mamun, A., Hulcová, D., Marková, J., Kučera, T., Jun, D., Šafratová, M., Maříková, J., Andrisano, V., Jenčo, J., Kuneš, J., Martinez, A., Nováková, L., & Cahlíková, L. (2020). Functionalized aromatic esters of the Amaryllidaceae alkaloid haemanthamine and their in vitro and in silico biological activity connected to Alzheimer’s disease. Bioorganic Chemistry, 100, 103928. 10.1016/j.bioorg.2020.103928 |
| Doi | 10.1016/j.bioorg.2020.103928 |
| Publication Date | Jul 2020 |
| Publication Type | Article |
| Researcher | Ana Martínez |
| Ontology | Computational models and simulations |
| Research Groups | Translational Medicinal and Biological Chemistry |
| Tools |