Synthesis and biological evaluation of quercetin and resveratrol peptidyl derivatives as potential anticancer and antioxidant agents

Amino Acids. 2019 Feb;51(2):319-329. doi: 10.1007/s00726-018-2668-6. Epub 2018 Nov 3.

Abstract

Quercetin and resveratrol are polyphenolic compounds, members of the flavonoid and the stilbene family, respectively, both medicinally important as dietary anticancer and antioxidant agents. They are present in a variety of foods-including fruits, vegetables, tea, wine, as well as other dietary supplements-and are responsible for various health benefits. Different quercetin and resveratrol esters of Leu/Met-enkephalin and tetrapeptide Leu-Ser-Lys-Leu (LSKL) were synthesized as model systems for monitoring the influence of the peptides on biological activity of resveratrol and quercetin. General formula of the main peptidyl-quercetin derivatives is 2-[3-(aa)n-4-hydroxyphenyl]-3,5,7-tri-hydroxy-4H-1-benzopyran-4-on, and the general formula of the main peptidyl-resveratrol derivatives is (E)-5-[4-(aa)n)styryl]benzene-1,3-diol. The antioxidant and anticancer activities of prepared compounds were investigated. Significant anticancer activity was obtained for the LSKL-based both quercetin and resveratrol derivatives. All prepared compounds exhibit antioxidant activity, in particular quercetin derivative containing Met-enkephalin.

Keywords: Leucine enkephalin; Methionine enkephalin; Quercetin; Resveratrol; Tetrapeptide LSKL.

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Antioxidants / chemical synthesis
  • Antioxidants / pharmacology*
  • Antioxidants / therapeutic use
  • Cell Proliferation / drug effects
  • Chromatography, High Pressure Liquid
  • Dietary Supplements
  • Enkephalin, Leucine / chemistry
  • Enkephalin, Methionine / chemistry
  • Esters / chemical synthesis
  • HCT116 Cells
  • Humans
  • MCF-7 Cells
  • Neoplasms / diet therapy*
  • Peptides / chemistry
  • Phytochemicals / chemical synthesis
  • Quercetin / analogs & derivatives*
  • Quercetin / chemical synthesis
  • Quercetin / pharmacology*
  • Quercetin / therapeutic use
  • Resveratrol / analogs & derivatives*
  • Resveratrol / chemical synthesis
  • Resveratrol / pharmacology*
  • Resveratrol / therapeutic use
  • Solubility
  • Transforming Growth Factor beta / metabolism

Substances

  • Antineoplastic Agents
  • Antioxidants
  • Esters
  • Leu-Ser-Lys-Leu peptide
  • Peptides
  • Phytochemicals
  • Transforming Growth Factor beta
  • Enkephalin, Methionine
  • Enkephalin, Leucine
  • Quercetin
  • Resveratrol