کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1356651 | 981144 | 2008 | 12 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Synthesis, structure–activity relationships and molecular modeling studies of new indole inhibitors of monoamine oxidases A and B Synthesis, structure–activity relationships and molecular modeling studies of new indole inhibitors of monoamine oxidases A and B](/preview/png/1356651.png)
New monoamine oxidase inhibitors were synthesized as indole analogues of a previously reported pyrrole series. Several compounds were potent MAO-A (12, 17, 19–22, 31, 36, and 37) or MAO-B (14, 20, 24, 38, 44, and 46) inhibitors, and had Ki values in the nanomolar concentration range. In particular, 22 (Ki = 0.00092 μM, and SI = 68,478) was exceptionally potent and selective as MAO-A inhibitor. In molecular modeling studies, compounds 22, 24, 44, and 46 positioned the indole ring into an aromatic cavity of MAO-A, and established π–π stacking interactions with Tyr407, Tyr444, and FAD cofactor. However, only compound 22 was able to form hydrogen bonds with FAD, a finding which was in accordance with its potent anti-MAO-A activity. Conversely, 22/MAOB complex was highly unstable during the MD simulation.
Figure optionsDownload as PowerPoint slide
Journal: Bioorganic & Medicinal Chemistry - Volume 16, Issue 22, 15 November 2008, Pages 9729–9740