Quercetin 3,7-dimethyl ether: a vasorelaxant flavonoid isolated from Croton schiedeanus Schlecht

J Pharm Pharmacol. 2002 Oct;54(10):1373-8. doi: 10.1211/002235702760345455.


The vasorelaxant profile of quercetin 3,7-dimethyl ether, a flavonoid isolated from Croton schiedeanus Schlecht (Euphorbiaceae), was assessed in aortic rings isolated from Wistar rats. To gain insight into its structure-activity relationship, we compared this substance with quercetin 3,4',7-trimethyl ether (ayanin), another flavonoid isolated from this plant, quercetin 3,3',4',7-tetramethyl ether, a flavonoid synthesized by us, and quercetin. In addition we examined the interaction of quercetin 3,7-dimethyl ether with the nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) pathway. According to their pEC50 values (concentration producing a 50% inhibition of the maximal contractile response) to phenylephrine-induced precontraction in rat isolated aorta, the potency order was quercetin 3,7-dimethyl ether > quercetin > quercetin 3,4',7-trimethyl ether > quercetin 3,3',4',7-tetramethyl ether (4.70+/-0.18; 3.96+/-0.07; 3.64+/-0.02; 3.11+/-0.16). The relaxant effect of quercetin 3,7-dimethyl ether was significantly decreased by the removal of endothelium as well as by methylene blue, an inhibitor of guanylyl cyclase, and by N(G)-nitro-L-arginine methyl ester hydrochloride (L-NAME), an NO-synthase inhibitor. Therefore, quercetin 3,7-dimethyl ether has a NO/cGMP pathway-related profile, with increased vasorelaxant activity due to hydroxylation at positions 3 and 4 of the B ring. In addition, methylation at positions 3 and 7 with respect to quercetin of the C and A rings, respectively, seems to further enhance the vasorelaxant activity of quercetin 3,7-dimethyl ether.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aorta, Thoracic / drug effects
  • Croton / chemistry*
  • Cyclic GMP / metabolism
  • Endothelium, Vascular / physiology
  • Enzyme Inhibitors / pharmacology
  • Flavonoids / isolation & purification
  • Flavonoids / pharmacology*
  • In Vitro Techniques
  • Magnetic Resonance Spectroscopy
  • Muscle Relaxation / drug effects
  • Muscle, Smooth, Vascular / drug effects*
  • NG-Nitroarginine Methyl Ester / pharmacology
  • Nitric Oxide / metabolism
  • Phenylephrine / pharmacology
  • Quercetin / analogs & derivatives
  • Quercetin / isolation & purification
  • Quercetin / pharmacology*
  • Rats
  • Rats, Wistar
  • Structure-Activity Relationship
  • Vasoconstrictor Agents / pharmacology
  • Vasodilator Agents / isolation & purification
  • Vasodilator Agents / pharmacology*


  • Enzyme Inhibitors
  • Flavonoids
  • Vasoconstrictor Agents
  • Vasodilator Agents
  • Phenylephrine
  • 3,7-dimethoxy-5,3',4'-trihydroxyflavone
  • Nitric Oxide
  • Quercetin
  • Cyclic GMP
  • NG-Nitroarginine Methyl Ester