title: Structure-activity relationship of the inhibitory effects of flavonoids on nitric oxide production in RAW264.7 cells.
abstract: 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 q2value 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.
authors.affiliation: School of Pharmacy, Nihon University, 7-7-1 Narashino-dai, Funabashi-shi, Chiba 274-8555, Japan.
authors.forename: Wen-Jun
authors.initials: WJ
authors.lastname: Jiang
authors.affiliation: School of Pharmacy, Nihon University, 7-7-1 Narashino-dai, Funabashi-shi, Chiba 274-8555, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Daikonya
authors.affiliation: School of Pharmacy, Nihon University, 7-7-1 Narashino-dai, Funabashi-shi, Chiba 274-8555, Japan.
authors.forename: Mitsuyoshi
authors.initials: M
authors.lastname: Ohkawara
authors.affiliation: School of Pharmacy, Nihon University, 7-7-1 Narashino-dai, Funabashi-shi, Chiba 274-8555, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Nemoto
authors.affiliation: School of Pharmacy, Nihon University, 7-7-1 Narashino-dai, Funabashi-shi, Chiba 274-8555, Japan.
authors.forename: Ryusuke
authors.initials: R
authors.lastname: Noritake
authors.affiliation: School of Pharmacy, Nihon University, 7-7-1 Narashino-dai, Funabashi-shi, Chiba 274-8555, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Takamiya
authors.affiliation: School of Pharmacy, Nihon University, 7-7-1 Narashino-dai, Funabashi-shi, Chiba 274-8555, Japan.
authors.forename: Susumu
authors.initials: S
authors.lastname: Kitanaka
authors.affiliation: School of Pharmacy, Nihon University, 7-7-1 Narashino-dai, Funabashi-shi, Chiba 274-8555, Japan. Electronic address: iijima.hiroshi@nihon-u.ac.jp.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Iijima
mesh_terms: D000818:Animals; D001688:Biological Products / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005419:Flavonoids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D051379:Mice; D008958:Models, Molecular; D015394:Molecular Structure; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D000067996:RAW 264.7 Cells; D029771:Rhodiola / Q000737:chemistry; D029909:Sophora / Q000737:chemistry; D013329:Structure-Activity Relationship
chemical_list: D001688:Biological Products; D005419:Flavonoids; D009569:Nitric Oxide
keywords: Comparative molecular field analysis; Flavonoid; Macrophage; Nitric oxide; Structure-activity relationship