Structure-activity relationship of the inhibitory effects of flavonoids on nitric oxide production in RAW264.7 cells

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• 作者：Wen-Jun Jiang ; Akihiro Daikonya¹ ; Mitsuyoshi Ohkawara ; Takashi Nemoto ; Ryusuke Noritake ; Tomoko Takamiya ; Susumu Kitanaka ; Hiroshi Iijima ; ^{iijima.hiroshi@nihon-u.ac.jp}
• 关键词：CoMFA ; comparative molecular field analysis ; IFN-γ ; interferon- ; LPS ; lipopolysaccharide ; NO ; nitric oxide
• 刊名：Bioorganic & Medicinal Chemistry
• 出版年：2017
• 出版时间：15 January 2017
• 年：2017
• 卷：25
• 期：2
• 页码：779-788
• 全文大小：1441 K
• 卷排序：25

文摘

We isolated flavonoids from herbal specimens from the Tibetan region (Sophora yunnanensis and Rhodiola sacra) that suppress nitric oxide (NO) production in macrophages stimulated by lipopolysaccharide and interferon-γ. The isolated flavonoids carry symmetric substitutions in the B ring (R3′ = R5′). We analyzed the quantitative structure-activity relationship of the inhibitory activity by comparative molecular field analysis (CoMFA) using this series of flavonoids. Use of flavonoids with symmetrical substitutions in the B ring made it simpler to align molecules because it was not necessary to consider a huge number of combinations due to the B-ring conformation. The CoMFA model, whose cross-validated q2 value was 0.705, suggested the existence of a hydroxy group at the 5-position, the choice of the A/C-ring scaffold (chromane or chromene) and electrostatic field around the B ring are important for NO inhibitory activity. Flavonoids synthesized based on the CoMFA model exhibited significant inhibitory potential against NO production, validating the predictive capability of the CoMFA model.