| Autor: |
Dong Wang, Ren-Yuan Hong, Mengyao Guo, Yi Liu, Nianhang Chen, Xun Li, De-Xin Kong |
| Jazyk: |
angličtina |
| Rok vydání: |
2019 |
| Předmět: |
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| Zdroj: |
Molecules, Vol 24, Iss 21, p 4003 (2019) |
| Druh dokumentu: |
article |
| ISSN: |
1420-3049 |
| DOI: |
10.3390/molecules24214003 |
| Popis: |
There is a continued need to develop new selective human monoamine oxidase (hMAO) inhibitors that could be beneficial for the treatment of neurological diseases. However, hMAOs are closely related with high sequence identity and structural similarity, which hinders the development of selective MAO inhibitors. “Three-Dimensional Biologically Relevant Spectrum (BRS-3D)” method developed by our group has demonstrated its effectiveness in subtype selectivity studies of receptor and enzyme ligands. Here, we report a series of novel C7-substituted coumarins, either synthesized or commercially purchased, which were identified as selective hMAO inhibitors. Most of the compounds demonstrated strong activities with IC50 values (half-inhibitory concentration) ranging from sub-micromolar to nanomolar. Compounds, FR1 and SP1, were identified as the most selective hMAO-A inhibitors, with IC50 values of 1.5 nM (selectivity index (SI) < −2.82) and 19 nM (SI < −2.42), respectively. FR4 and FR5 showed the most potent hMAO-B inhibitory activity, with IC50 of 18 nM and 15 nM (SI > 2.74 and SI > 2.82). Docking calculations and molecular dynamic simulations were performed to elucidate the selectivity preference and SAR profiles. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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