論文

査読有り 国際誌
2019年11月

2-Styrylchromone derivatives as potent and selective monoamine oxidase B inhibitors.

Bioorganic chemistry
  • Koichi Takao
  • ,
  • Saki Endo
  • ,
  • Junko Nagai
  • ,
  • Hitoshi Kamauchi
  • ,
  • Yuri Takemura
  • ,
  • Yoshihiro Uesawa
  • ,
  • Yoshiaki Sugita

92
開始ページ
103285
終了ページ
103285
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1016/j.bioorg.2019.103285

A series of eighteen 2-styrylchromone derivatives (see Chart 1) were synthesized and evaluated for their monoamine oxidase (MAO) A and B inhibitory activities. Many of the derivatives inhibited MAO-B comparable to pargyline (a positive control), and most of them inhibited MAO-B selectively. Of the eighteen derivatives, compound 9 having methoxy group at R1 and chlorine at R4 showed both the best MAO-B inhibitory activity (IC50 = 17 ± 2.4 nM) and the best MAO-B selectivity (IC50 for MAO-A/IC50 for MAO-B = 1500). The mode of inhibition of compound 9 against MAO-B was competitive and reversible. Quantitative structure-activity relationship (QSAR) analyses of the 2-styrylchromone derivatives were conducted using their pIC50 values with the use of Molecular Operating Environment (MOE) and Dragon, demonstrating that the descriptors of MAO-B inhibitory activity and MAO-B selectivity were 1734 and 121, respectively, that showed significant correlations (P < 0.05). We then examined the 2-styrylchromone structures as useful scaffolds through three-dimensional-QSAR studies using AutoGPA, which is based on the molecular field analysis algorithm using MOE. The model using pIC50 value indexes for MAO-B exhibited a determination coefficient (R2) of 0.873 as well as a Leave-One-Out cross-validated determination coefficient (Q2) of 0.675. These data suggested that the 2-styrylchromone structure might be a useful scaffold for the design and development of novel MAO-B inhibitors.

リンク情報
DOI
https://doi.org/10.1016/j.bioorg.2019.103285
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/31561103
ID情報
  • DOI : 10.1016/j.bioorg.2019.103285
  • PubMed ID : 31561103

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