title: Synthesis of glabridin derivatives as tyrosinase inhibitors.
abstract: A novel 3'',4''-dihydroglabridin was successfully prepared for studying on tyrosinase inhibitory activity. The result demonstrated that 3'',4''-dihydroglabridin exhibited higher activity than glabridin (IC(50) value = 11.40 microM), which is probably due to the 4-substituted resorcinol skeleton and the lacking of double bond between carbon atom 3'' and 4'' on its structure giving more conformational flexibily to interact with the enzyme more effectively. In addition, various acylated derivatives were synthesized as glabridin prodrugs. The chemical and enzymatic hydrolysis of prodrugs revealed that the diacetate ester was rapidly hydrolyzed by porcine liver esterase with the half-life of 2.36 minute, while those of the dihexanoate was 14.8 hour. Both of them were sufficiently stable in phosphate buffer, both pH 5.5 and 7.4, at 37 degrees C with more than 15 days half-life.
authors.affiliation: Department of Pharmaceutical Chemistry, Chulalongkorn University, Bangkok, 10330, Thailand.
authors.forename: Warunee
authors.initials: W
authors.lastname: Jirawattanapong
authors.forename: Ekarin
authors.initials: E
authors.lastname: Saifah
authors.forename: Chamnan
authors.initials: C
authors.lastname: Patarapanich
mesh_terms: D000215:Acylation; D000363:Agaricales / Q000201:enzymology; D000588:Amines / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D004355:Drug Stability; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D004950:Esterases / Q000378:metabolism; D006207:Half-Life; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D007700:Kinetics; D008099:Liver / Q000201:enzymology; D015394:Molecular Structure; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors* / Q000302:isolation & purification; D011355:Prodrugs / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013552:Swine; D013696:Temperature
chemical_list: D000588:Amines; D004791:Enzyme Inhibitors; D011355:Prodrugs; C044849:glabrin; D014442:Monophenol Monooxygenase; D004950:Esterases