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

Akihiro Tai, Satomi Goto, Yutaka Ishiguro, Kazuko Suzuki, Teruhiko Nitoda, Itaru Yamamoto

Research output: Contribution to journal › Article

25 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)623-627
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Volume14
Issue number3
DOIs
Publication statusPublished - Feb 9 2004

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Metabolism
Permeation
Ascorbic Acid
Skin
Derivatives
Permeability
Prodrugs
Metabolites
Metabolic Networks and Pathways

Keywords

  • Lipophilic ascorbate (6-Acyl-AA-2G)
  • Skin permeation
  • Stable ascorbate (AA-2G)

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Organic Chemistry
  • Drug Discovery
  • Pharmaceutical Science

Cite this

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. / Tai, Akihiro; Goto, Satomi; Ishiguro, Yutaka; Suzuki, Kazuko; Nitoda, Teruhiko; Yamamoto, Itaru.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 14, No. 3, 09.02.2004, p. 623-627.

Research output: Contribution to journal › Article

Tai, A, Goto, S, Ishiguro, Y, Suzuki, K, Nitoda, T & Yamamoto, I 2004, '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', Bioorganic and Medicinal Chemistry Letters, vol. 14, no. 3, pp. 623-627. https://doi.org/10.1016/j.bmcl.2003.11.059
Tai A, Goto S, Ishiguro Y, Suzuki K, Nitoda T, Yamamoto I. 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. Bioorganic and Medicinal Chemistry Letters. 2004 Feb 9;14(3):623-627. https://doi.org/10.1016/j.bmcl.2003.11.059
Tai, Akihiro ; Goto, Satomi ; Ishiguro, Yutaka ; Suzuki, Kazuko ; Nitoda, Teruhiko ; Yamamoto, Itaru. / 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. In: Bioorganic and Medicinal Chemistry Letters. 2004 ; Vol. 14, No. 3. pp. 623-627.
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abstract = "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.",
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