Synthesis and structure-activity relationships of polymethoxyflavones aimed at application to medical therapy of eye disease

2014 Fiscal Year Final Research Report

• Project/Area Number: 24590146
• 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, 准教授 (00279043)
• Co-Investigator(Kenkyū-buntansha): KOSANO Hiroshi 帝京大学, 薬学部, 教授 (40246020)
• Co-Investigator(Renkei-kenkyūsha): MIYATA Yoshiki 帝京大学, 薬学部, 講師 (20433881) ; TABATA Hidetsugu 帝京大学, 薬学部, 助教 (80445634)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: ポリメトキシフラボン / 構造活性相関 / MMP-9 / 白内障 / 糖尿病網膜症 / 血液網膜関門

Outline of Final Research Achievements

Over the past two decades, increasing attention has been given to polymethoxyflavones (PMFs). Among them, nobiletin, one of the most abundant PMFs in citrus peel, has been of particular interest and its diverse properties beneficial to health have been reported by many research groups. However, systematic studies on the structure-activity relationships of PMFs have not been widely reported, with a few exceptions. we succeeded in developing a new synthetic method for nobiletin metabolites and congeners, which involves easier access to the highly oxygenated A-ring moiety. The synthesized PMFs showed potent inhibitory activity against pro-matrix metalloproteinase(MMP)-9 production on lens epithelial cells (LECs). Since MMP-9 expression plays an important role in various pathological states including cataract, tumor metastasis, etc., these compounds could be potent lead for chemotherapeutic agents for the treatment of those diseases.

Free Research Field

有機合成化学