Synthetic study on polymethoxyflavones: separation and enhancing of their biological activities

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K08032
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Drug development chemistry
• Research Institution: Teikyo University
• Principal Investigator: Oshitari Tetsuta 帝京大学, 薬学部, 教授 (00279043)
• Co-Investigator(Kenkyū-buntansha): 小佐野 博史 帝京大学, 薬学部, 教授 (40246020)
• Co-Investigator(Renkei-kenkyūsha): Miyata Yoshiki 帝京大学, 薬学部, 准教授 (20433881) ; Tabata Hidetsugu 帝京大学, 薬学部, 講師 (80445634)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: ポリメトキシフラボン / 後発白内障 / 糖尿病網膜症 / 構造活性相関 / MMP-9

Outline of Final Research Achievements

Over the past two decades, increasing attention has been given to polymethoxyflavones (PMFs) because of their diverse bioactivities such as anticancer, antiinflammatory, antidiabetic, and neurotrophic activities. We demonstrated that nobiletin isolated from citrus plants attenuated MMP-9 enzymatic activity through the suppression of transcription for MMP-9 gene and augmentation of TIMP-1 production in retinal Mueller cells. Nobiletin regulated MMP-9 gene expression and TIMP-1 by inhibiting the PI3 K/Akt signaling pathway. We also observed the augmentation of inhibitory action against MMP-9 activity by 4'-demethylnobiletin. We believe that the enhancement of inhibitory action against MMP-9 activity by 4'-demethylnobiletin is through the dual inhibition on Erk1/2 and Akt phosphorylation. The SAR studies revealed that, for the enhancement of inhibitory action against MMP-9 enzymatic activity, demethylation at position 4' in B-ring was a key structural modification in Mueller cells.

Free Research Field

医薬品化学、有機合成化学