Increased Bioavailability of Tricin−Amino Acid Derivatives via a Prodrug Approach.

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. [ABSTRACT FROM AUTHOR]