Design, Synthesis and Biological Evaluation of 5-Hydroxy-2-(3-phenylpropyl) Chromone Derivatives as 5-HT28 Receptor Ligands
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Authors
Kim, Min Soo
Issue Date
2018
Type
Thesis
Language
en_US
Keywords
Alternative Title
Abstract
Serotonin(5-HT)and its receptors are involved in a wide range of physiological functions. The serotonin receptor 2 (5-HT2)in particular, is known to interact with many psychopharmaceuticals. This clinical significance indicates that designingligands targeting the 5-HT2receptors may allow useful therapeutic exploitation. A recently isolated natural compound, 5-hydroxy-2-(2-phenylethyl) chromone (5-HPEC)has shown to be a 5-HT2Bantagonist and also possess neuroprotective properties in rat cortical cell cultures. Studies on 5-HPEC optimization led to a novel compound,5-hydroxy-2-(3-phenylpropyl) chromone (5-HPPC), which showed improved inhibition and affinity against 5-HT2B. This study aimed to design 5-HT2Bligands by modifying the 5-HPPC scaffold to further enhance its affinity and selectivity towards the receptor. Compounds with varying substituents on C-3, C-3′,and C-4′were synthesized, characterized and biologically evaluated. Among the derivatives, 5-hydroxy-2-(3-(3-cyanophenyl) propyl) chromone emerged as a new lead compound with 4-fold improvement in binding affinity over 5-HPPC. Computational data from ligand docking studies on compounds with promising profiles also confirmed the biological data. Potential improvements of the new lead were proposed based on the ligand docking results.
Description
viii, 29 p.
Citation
Publisher
Kalamazoo College
License
U.S. copyright laws protect this material. Commercial use or distribution of this material is not permitted without prior written permission of the copyright holder. All rights reserved.