title: Increased bioavailability of tricin-amino acid derivatives via a prodrug approach.
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.
authors.affiliation: Department of Materials Science and Technology, Faculty of Engineering, School of Medicine, Gifu University, 1-1 Yanagido, Gifu 501-1194, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Ninomiya
authors.forename: Kaori
authors.initials: K
authors.lastname: Tanaka
authors.forename: Yuzo
authors.initials: Y
authors.lastname: Tsuchida
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Muto
authors.forename: Mamoru
authors.initials: M
authors.lastname: Koketsu
authors.forename: Kunitomo
authors.initials: K
authors.lastname: Watanabe
mesh_terms: D000284:Administration, Oral; D000409:Alanine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D001682:Biological Availability; D002460:Cell Line; D002463:Cell Membrane Permeability; D003587:Cytomegalovirus; D004285:Dogs; D004355:Drug Stability; D005419:Flavonoids / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D018698:Glutamic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D008297:Male; D011355:Prodrugs / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: D000998:Antiviral Agents; D005419:Flavonoids; D011355:Prodrugs; D018698:Glutamic Acid; C017769:tricin; D000409:Alanine