Synthesis and biological evaluation of 3-styrylchromone derivatives as selective monoamine oxidase B inhibitors.

Bioorganic & Medicinal Chemistry
Koichi TakaoYoshiaki Sugita

Abstract

A series of 3-styrylchromone derivatives was synthesized and evaluated for monoamine oxidase (MAO) A and B inhibitory activities. Most of all derivatives inhibited MAO-B selectively, except compound 21. Compound 19, which had a methoxy group at R2 on the chromone ring and chlorine at R4 on phenyl ring, potently inhibited MAO-B, with an IC50 value of 2.2 nM. Compound 1 showed the highest MAO-B selectivity, with a selectivity index of >3700. Further analysis of these compounds indicated that compounds 1 and 19 were reversible and mixed-type MAO-B inhibitors, suggesting that their mode of action may be through tight-binding inhibition to MAO-B. Quantitative structure-activity relationship (QSAR) analyses of the 3-styrylchromone derivatives were conducted using their pIC50 values, through Molecular Operating Environment (MOE) and Dragon. There were 1796 descriptors of MAO-B inhibitory activity, which showed significant correlations (P < 0.05). Further investigation of the 3-styrylchromone structures as useful scaffolds was performed through three-dimensional-QSAR studies using AutoGPA, which is based on the molecular field analysis algorithm using MOE. The MAO-B inhibitory activity model constructed using pIC50 value index exhibite...Continue Reading

References

Jun 24, 2011·Journal of Medicinal Chemistry·Alexandra GasparFernanda Borges
Feb 22, 2014·Chemical Reviews·Alexandra GasparFernanda Borges
Oct 12, 2016·Chemical & Pharmaceutical Bulletin·Koichi TakaoYoshiaki Sugita
May 26, 2017·Journal of Medicinal Chemistry·Joana ReisFernanda Borges
Apr 11, 2018·Journal of Neural Transmission·Keith F Tipton
Sep 1, 2018·Journal of Neural Transmission·Luca Giacinto IacovinoClaudia Binda
Sep 18, 2020·European Journal of Medicinal Chemistry·Shoaib Manzoor, Nasimul Hoda
Nov 3, 2020·Chemical & Pharmaceutical Bulletin·Koichi TakaoYoshiaki Sugita

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