Cyclopropane derivatives as potential human serine racemase inhibitors: unveiling novel insights into a difficult target
| العنوان: | Cyclopropane derivatives as potential human serine racemase inhibitors: unveiling novel insights into a difficult target |
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| المؤلفون: | Chiara Pecchini, Chiara Cocconcelli, Andrea Mozzarelli, Gabriele Costantino, Barbara Campanini, Claudia Beato, Marco Pieroni, Marialaura Marchetti |
| المصدر: | Journal of enzyme inhibition and medicinal chemistry 31 (2016): 645–652. doi:10.3109/14756366.2015.1057720 info:cnr-pdr/source/autori:Beato C, Pecchini C, Cocconcelli C, Campanini B, Marchetti ML, Pieroni M, Mozzarelli A, Costantino G/titolo:Cyclopropane derivatives as potential human serine racemase inhibitors: unveiling novel insights into a difficult target/doi:10.3109%2F14756366.2015.1057720/rivista:Journal of enzyme inhibition and medicinal chemistry (Print)/anno:2016/pagina_da:645/pagina_a:652/intervallo_pagine:645–652/volume:31 |
| بيانات النشر: | Taylor & Francis, 2016. |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | Cyclopropanes, 0301 basic medicine, Stereochemistry, Racemases and Epimerases, Malonic acid, Inhibitory postsynaptic potential, Cyclopropane, Structure-Activity Relationship, 03 medical and health sciences, chemistry.chemical_compound, Drug Discovery, Humans, Enzyme Inhibitors, Inhibition, Binding affinities, Pharmacology, chemistry.chemical_classification, Dose-Response Relationship, Drug, Molecular Structure, General Medicine, Molecular Docking Simulation, Serine recemase, 030104 developmental biology, Dicarboxylic acid, chemistry, Biochemistry, Serine racemase, Molecular docking, Glycine, Conformational ensemble, NMDA receptor |
| الوصف: | d-Serine is the co-agonist of NMDA receptors and binds to the so-called glycine site. d-Serine is synthesized by human serine racemase (SR). Over activation of NMDA receptors is involved in many neurodegenerative diseases and, therefore, the inhibition of SR might represent a novel strategy for the treatment of these pathologies. SR is a very difficult target, with only few compounds so far identified exhibiting weak inhibitory activity. This study was aimed at the identification of novel SR inhibitor by mimicking malonic acid, the best-known SR inhibitor, with a cyclopropane scaffold. We developed, synthesized, and tested a series of cyclopropane dicarboxylic acid derivatives, complementing the synthetic effort with molecular docking. We identified few compounds that bind SR in high micromolar range with a lack of significant correlation between experimental and predicted binding affinities. The thorough analysis of the results can be exploited for the development of more potent SR inhibitors. |
| DOI: | 10.6084/m9.figshare.3203590 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1bf2077a646f095d4b3aa2fb0a0d310f |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....1bf2077a646f095d4b3aa2fb0a0d310f |
| قاعدة البيانات: | OpenAIRE |
| DOI: | 10.6084/m9.figshare.3203590 |
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