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

  • Bioorg Med Chem. 2017 Jan 15;25(2):779-788. doi: 10.1016/j.bmc.2016.11.055.
Wen-Jun Jiang  1 ,  Akihiro Daikonya  1 ,  Mitsuyoshi Ohkawara  1 ,  Takashi Nemoto  1 ,  Ryusuke Noritake  1 ,  Tomoko Takamiya  1 ,  Susumu Kitanaka  1 ,  Hiroshi Iijima  2
Affiliations
  • 1. School of Pharmacy, Nihon University, 7-7-1 Narashino-dai, Funabashi-shi, Chiba 274-8555, Japan.
  • 2. School of Pharmacy, Nihon University, 7-7-1 Narashino-dai, Funabashi-shi, Chiba 274-8555, Japan. Electronic address: [email protected].
PMID: 27955927 DOI: 10.1016/j.bmc.2016.11.055
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 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.

Keywords
Comparative molecular field analysis; Flavonoid; Macrophage; Nitric oxide; Structure-activity relationship.