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Design, synthesis, and vasorelaxant and platelet antiaggregatory activities of coumarin-resveratrol hybrids

Bioorg Med Chem Lett. 2006 Jan 15;16(2):257-61. doi: 10.1016/j.bmcl.2005.10.013. Epub 2005 Nov 3.

Abstract

We have synthesized the coumarin-resveratrol hybrid 4 and its dimethoxy derivative 3 by a very direct synthetic route involving a Pechmann procedure. Compound 4 has also been synthesized by an alternative route (Perkin), which also allowed the synthesis of compounds 9-13. In addition, we have evaluated the potential vasorelaxant activity of the new compounds in endothelium-containing rat aorta rings pre-contracted with noradrenaline, as well as the inhibitory effects on platelet aggregation induced by thrombin in washed human platelets. The compounds reported here relaxed vascular smooth muscle and inhibited platelet aggregation with a profile similar to that of trans-resveratrol (t-RESV) and, in some cases, showed activity higher than that of the natural compound. This is the case for compound 13, which has a vasorelaxant activity that is twice as high as that of t-resveratrol and a platelet antiaggregant activity that is six times higher. These results suggest that these novel compounds may have potential as structural templates for the design and subsequent development of new vasodilatory and platelet antiaggregatory drugs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aorta, Thoracic / drug effects
  • Blood Platelets / drug effects
  • Coumarins* / chemical synthesis
  • Coumarins* / chemistry
  • Coumarins* / pharmacology
  • Drug Design
  • Drug Evaluation, Preclinical
  • Humans
  • Molecular Structure
  • Muscle, Smooth, Vascular / drug effects
  • Norepinephrine / antagonists & inhibitors
  • Norepinephrine / pharmacology
  • Platelet Aggregation / drug effects*
  • Platelet Aggregation Inhibitors* / chemical synthesis
  • Platelet Aggregation Inhibitors* / chemistry
  • Platelet Aggregation Inhibitors* / pharmacology
  • Rats
  • Resveratrol
  • Stilbenes* / chemical synthesis
  • Stilbenes* / chemistry
  • Stilbenes* / pharmacology
  • Thrombin / antagonists & inhibitors
  • Thrombin / pharmacology
  • Time Factors
  • Vasodilator Agents* / chemical synthesis
  • Vasodilator Agents* / chemistry
  • Vasodilator Agents* / pharmacology
  • Vasomotor System / drug effects*
  • Vasomotor System / physiology

Substances

  • Coumarins
  • Platelet Aggregation Inhibitors
  • Stilbenes
  • Vasodilator Agents
  • coumarin
  • Thrombin
  • Resveratrol
  • Norepinephrine