56297-98-4Relevant articles and documents
Synthesis, biological evaluation, and molecular docking of dihydroflavonol derivatives as anti-inflammatory agents
Xiang, Yuanhang,Hu, Chunling,Zhang, Yuejie,Ye, Xiaochuan
, p. 863 - 872 (2019/04/17)
A series of dihydroflavonol derivatives (4a–4l) were synthesized from chalcones via classical Algar–Flynn–Oyamada (AFO) reaction and characterized on the basis of spectroscopic analyses. All synthesized compounds were evaluated for their inhibitory activity against the pro-inflammatory-inducible TNF-alpha, IL-1beta, and IL-6 in lipopolysaccharide (LPS)-stimulated RAW 264.7 cell lines and showed various efficiency. Furthermore, compounds 4d and 4k were selected to examine their in vivo anti-inflammatory activity by using two classical models. Herein compound 4k showed maximum anti-inflammatory activity of 32.98% inhibition in mice ear-swelling model and 40.06% inhibition at the 2 h intervals in rat paw edema model in comparison to the two references: aspirin and meloxicam. Similar effect was observed at a lower dose. In addition, the compound 4k was docked against cyclooxygenases-2 to validate the attained pharmacological data and provide understandable evidence for the observed anti-inflammatory activity.
Development and Optimization of an in Vitro Multienzyme Synthetic System for Production of Kaempferol from Naringenin
Zhang, Zhiping,He, Yanzhi,Huang, Yue,Ding, Li,Chen, Lei,Liu, Yaxian,Nie, Yesen,Zhang, Xinyue
, p. 8272 - 8279 (2018/07/30)
An in vitro multienzyme synthetic system was developed and optimized to efficiently produce kaempferol in a single reaction tube. Two key genes, Atf3h and Atfls1, in the biosynthetic pathway of kaempferol were cloned into a prokaryotic expression vector and overexpressed in Escherichia coli. The recombinant proteins were purified through affinity chromatography and showed activities of flavanone 3-hydroxylase and flavonol synthase, respectively, followed by development of an in vitro synthetic system for producing kaempferol. The system contains 8.2 mM α-ketoglutaric acid, 0.01 mM ferrous ion, 0.4% sodium ascorbate, 25 μg/mL of each recombinant enzyme, and 10% glycerol in 100 mM Tris-HCl (pH 7.2). When the reaction was carried out at 40 °C for 40-50 min, the yield of kaempferol was 37.55 ± 1.62 mg/L and the conversion rate from NRN to KMF was 55.89% ± 2.74%. Overall, this system provides a promising and efficient approach to produce kaempferol economically.
Stereospecific inhibition of nitric oxide production in macrophage cells by flavanonols: Synthesis and the structure-activity relationship
Jiang, Wen-Jun,Ishiuchi, Kan'Ichiro,Furukawa, Megumi,Takamiya, Tomoko,Kitanaka, Susumu,Iijima, Hiroshi
, p. 6922 - 6929 (2015/11/11)
To explore the structure-activity relationships on the inhibitory activity of flavanonols against nitric oxide (NO) production in inflammatory cells, we synthesized 19 flavanonols which shared a common 3,5,7-trihydroxychroman scaffold. A range of substitutions was included in the B ring in order to investigate the structure-activity relationship. We also succeeded in isolating stereoisomers from 16 of the flavanonols using chiral column chromatography. The inhibitory effects of these compounds on NO production were examined in RAW 264.7 cells (a murine macrophage-like cell line), which were activated by lipopolysaccharide (LPS). We only observed inhibitory activity against NO production in (2R,3R) stereoisomers, while the inhibitory activities of (2S,3S) stereoisomers were significantly weaker. We also evaluated the free radical scavenging potential of the flavanonols using 1,1-diphenyl-2-picrylhydrazyl (DPPH). Each stereoisomer indicated the equivalent DPPH scavenging potential as expected. The radical scavenging activity was not correlated with the inhibitory activity against NO. The inhibition of NO production by flavanonols is stereospecific and cannot simply be explained by their radical scavenging activity. We propose the possible existence of a 'target' molecule for flavanonols which is involved in the production and/or regulation of NO in RAW 264.7 cells.
