In vitro evaluation of quercetin-3-O-acyl esters as topical prodrugs.
Quercetin-3-O-acyl esters (I-VI) were synthesized and their usefulness as quercetin topical prodrugs was evaluated. Quercetin esters were assayed to determine their water stability and solubility, their susceptibility to undergoing enzymatic hydrolysis and their permeation through excised human skin. Quercetin ethyl (I) and hexyl (IV) esters proved poorly stable in aqueous media and they were not assayed further. Among the derivatives tested, quercetin propyl (II) and butyl (III) esters were more water-soluble than the parent drug. Esters II, III and V were readily hydrolyzed by human plasma and esters II and III penetrated excised human skin better than quercetin from aqueous saturated solutions. On the basis of the results obtained, esters II and III could be regarded as promising quercetin topical prodrugs.
Montenegro
Lucia
L
Department of Pharmaceutical Sciences, University of Catania, V.le A.Doria 6, Catania I-95125, Italy. lmontene@unict.it
Carbone
Claudia
C
Maniscalco
Claudio
C
Lambusta
Daniela
D
Nicolosi
Giovanni
G
Ventura
Cinzia A
CA
Puglisi
Giovanni
G
D000279:Administration, Cutaneous; D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D004952:Esters / Q000138:chemical synthesis / Q000737:chemistry*; D005419:Flavonoids / Q000138:chemical synthesis / Q000737:chemistry*; D006207:Half-Life; D006801:Humans; D006868:Hydrolysis; D057927:Hydrophobic and Hydrophilic Interactions; D010539:Permeability; D011355:Prodrugs / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D011794:Quercetin / Q000737:chemistry* / Q000493:pharmacokinetics; D012867:Skin / Q000378:metabolism; D012869:Skin Absorption; D012995:Solubility; D013329:Structure-Activity Relationship
D004952:Esters; D005419:Flavonoids; D011355:Prodrugs; D011794:Quercetin