TY - JOUR
T1 - Permeation and metabolism of a series of novel lipophilic ascorbic acid derivatives, 6-O-acyl-2-O-α-D-glucopyranosyl-L-ascorbic acids with a branched-acyl chain, in a human living skin equivalent model
AU - Tai, Akihiro
AU - Goto, Satomi
AU - Ishiguro, Yutaka
AU - Suzuki, Kazuko
AU - Nitoda, Teruhiko
AU - Yamamoto, Itaru
N1 - Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2004/2/9
Y1 - 2004/2/9
N2 - A series of novel lipophilic vitamin C derivatives, 6-O-acyl-2-O-α-D- glucopyranosyl-L-ascorbic acids possessing a branched-acyl chain of varying length from C8 to C16 (6-bAcyl-AA-2G), were evaluated as topical prodrugs of ascorbic acid (AA) with transdermal activity in a human living skin equivalent model. The permeability of 6-bAcyl-AA-2G was compared with those of the derivatives having a straight-acyl chain (6-sAcyl-AA-2G). Out of 10 derivatives of 6-sAcyl-AA-2G and 6-bAcyl-AA-2G, 6-sDode-AA-2G and 6-bDode-AA-2G exhibited most excellent permeability in this model. Measurement of the metabolites permeated from the skin model suggested that 6-bDode-AA-2G was mainly hydrolyzed via 6-O-acyl AA to AA by tissue enzymes, while 6-sDode-AA-2G was hydrolyzed via 2-O-α-D-glucopyranosyl-L-ascorbic acid to AA. The former metabolic pathway seems to be advantageous for a readily available source of AA, because 6-O-acyl AA, as well as AA, is able to show vitamin C activity.
AB - A series of novel lipophilic vitamin C derivatives, 6-O-acyl-2-O-α-D- glucopyranosyl-L-ascorbic acids possessing a branched-acyl chain of varying length from C8 to C16 (6-bAcyl-AA-2G), were evaluated as topical prodrugs of ascorbic acid (AA) with transdermal activity in a human living skin equivalent model. The permeability of 6-bAcyl-AA-2G was compared with those of the derivatives having a straight-acyl chain (6-sAcyl-AA-2G). Out of 10 derivatives of 6-sAcyl-AA-2G and 6-bAcyl-AA-2G, 6-sDode-AA-2G and 6-bDode-AA-2G exhibited most excellent permeability in this model. Measurement of the metabolites permeated from the skin model suggested that 6-bDode-AA-2G was mainly hydrolyzed via 6-O-acyl AA to AA by tissue enzymes, while 6-sDode-AA-2G was hydrolyzed via 2-O-α-D-glucopyranosyl-L-ascorbic acid to AA. The former metabolic pathway seems to be advantageous for a readily available source of AA, because 6-O-acyl AA, as well as AA, is able to show vitamin C activity.
KW - Lipophilic ascorbate (6-Acyl-AA-2G)
KW - Skin permeation
KW - Stable ascorbate (AA-2G)
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U2 - 10.1016/j.bmcl.2003.11.059
DO - 10.1016/j.bmcl.2003.11.059
M3 - Article
C2 - 14741256
AN - SCOPUS:1642575100
VL - 14
SP - 623
EP - 627
JO - Bioorganic and Medicinal Chemistry Letters
JF - Bioorganic and Medicinal Chemistry Letters
SN - 0960-894X
IS - 3
ER -