Increased bioavailability of tricin-amino acid derivatives via a prodrug approach

J Med Chem. 2011 Mar 10;54(5):1529-36. doi: 10.1021/jm1015457. Epub 2011 Feb 14.

Abstract

Tricin (4',5,7-trihydroxy-3',5'-dimethoxyflavone) has demonstrated diverse biological activities. This compound has a high anti-human cytomegalovirus (HCMV) activity; however, its oral availability is low. To improve its bioavailability, we synthesized tricin-amino acid derivatives as prodrugs and investigated their cell permeability, stability in vitro, and oral availability in vivo. The results demonstrated that the tricin-alanine-glutamic acid conjugate exhibited enhanced permeability, stability in MDCK cells, and excellent bioavailability after oral administration in Crl:CD (SD) male rats. Tricin-alanine-glutamic acid conjugate is a potential new anti-HCMV drug.

MeSH terms

  • Administration, Oral
  • Alanine / analogs & derivatives*
  • Alanine / chemical synthesis*
  • Alanine / pharmacokinetics
  • Animals
  • Antiviral Agents / chemical synthesis*
  • Antiviral Agents / pharmacokinetics
  • Biological Availability
  • Cell Line
  • Cell Membrane Permeability
  • Cytomegalovirus
  • Dogs
  • Drug Stability
  • Flavonoids / chemical synthesis*
  • Flavonoids / pharmacokinetics
  • Glutamic Acid / analogs & derivatives*
  • Glutamic Acid / chemical synthesis*
  • Glutamic Acid / pharmacokinetics
  • Male
  • Prodrugs / chemical synthesis*
  • Prodrugs / pharmacokinetics
  • Rats
  • Structure-Activity Relationship

Substances

  • Antiviral Agents
  • Flavonoids
  • Prodrugs
  • Glutamic Acid
  • tricin
  • Alanine