Vasorelaxant effect of flavonoids through calmodulin inhibition: Ex vivo, in vitro, and in silico approaches

Bioorg Med Chem. 2011 Jan 1;19(1):542-6. doi: 10.1016/j.bmc.2010.10.063. Epub 2010 Nov 4.

Abstract

In our search for potential antihypertensive agents, a series of structurally-related flavonoids was screened. Ex vivo and in vitro biological evaluations indicated that compounds 1-7 displayed an important vasorelaxant effect on the endothelium-intact (E(+)) and -denuded (E(-)) aortic rings test. Their in vitro anti-calmodulin (CaM) properties were determined by means of the inhibitory effect on the activation of the calmodulin-sensitive cAMP phosphodiesterase (PDE1) assay. Molecular modeling experiments were also performed in order to explore the probable binding site of 1-7 with CaM, and the results indicated that they could bind to the protein in the same pocket as trifluoperazine (TFP), a well-known CaM inhibitor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aorta / drug effects*
  • Aorta / physiology
  • Calmodulin / antagonists & inhibitors*
  • Dose-Response Relationship, Drug
  • Flavonoids / chemistry
  • Flavonoids / pharmacology*
  • In Vitro Techniques
  • Models, Molecular
  • Rats
  • Rats, Wistar
  • Vasodilator Agents / chemistry
  • Vasodilator Agents / pharmacology*

Substances

  • Calmodulin
  • Flavonoids
  • Vasodilator Agents