| Autor: |
Kamil Kuca, Katarina Siposova, Lucie Drtinova, Zuzana Gazova, Ondrej Soukup, Kamil Musilek, Anna Horova, Katarina Spilovska, Jan Korabecny, Jan Kral |
| Jazyk: |
angličtina |
| Rok vydání: |
2013 |
| Předmět: |
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| Zdroj: |
Molecules, Vol 18, Iss 2, Pp 2397-2418 (2013) |
| Druh dokumentu: |
article |
| ISSN: |
1420-3049 |
| DOI: |
10.3390/molecules18022397 |
| Popis: |
A structural series of 7-MEOTA-adamantylamine thioureas was designed, synthesized and evaluated as inhibitors of human acetylcholinesterase (hAChE) and human butyrylcholinesterase (hBChE). The compounds were prepared based on the multi-target-directed ligand strategy with different linker lengths (n = 2–8) joining the well-known NMDA antagonist adamantine and the hAChE inhibitor 7-methoxytacrine (7-MEOTA). Based on in silico studies, these inhibitors proved dual binding site character capable of simultaneous interaction with the peripheral anionic site (PAS) of hAChE and the catalytic active site (CAS). Clearly, these structural derivatives exhibited very good inhibitory activity towards hBChE resulting in more selective inhibitors of this enzyme. The most potent cholinesterase inhibitor was found to be thiourea analogue 14 (with an IC50 value of 0.47 µM for hAChE and an IC50 value of 0.11 µM for hBChE, respectively). Molecule 14 is a suitable novel lead compound for further evaluation proving that the strategy of dual binding site inhibitors might be a promising direction for development of novel AD drugs. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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