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. 2021 Aug 3;26(15):4684.
doi: 10.3390/molecules26154684.

Antiallergic Activity of 6-Deoxy-2- O-methyl-6-(N-hexadecanoyl)amino-l-ascorbic Acid

Kaori Miura  1 , Hiroaki Matsuno  2 , Yuji Iwaoka  3 , Hideyuki Ito  3 , Akihiro Tai  2   4
Affiliations

Antiallergic Activity of 6-Deoxy-2- O-methyl-6-(N-hexadecanoyl)amino-l-ascorbic Acid

Kaori Miura et al. Molecules. .

Abstract

Allergy is an excessive immune response to a specific antigen. Type I allergies, such as hay fever and food allergies, have increased significantly in recent years and have become a worldwide problem. We previously reported that an ascorbic acid derivative having palmitoyl and glucosyl groups, 2-O-α-d-glucopyranosyl-6-O-hexadecanoyl-l-ascorbic acid (6-sPalm-AA-2G), showed inhibitory effects on degranulation in vitro and on the passive cutaneous anaphylaxis (PCA) reaction in mice. In this study, several palmitoyl derivatives of ascorbic acid were synthesized and a structure-activity relationship study was performed to discover more potent ascorbic acid derivatives with degranulation inhibitory activity. 6-Deoxy-2-O-methyl-6-(N-hexadecanoyl)amino-l-ascorbic acid (2-Me-6-N-Palm-AA), in which a methyl group was introduced into the hydroxyl group at the C-2 position of ascorbic acid and in which the hydroxyl group at the C-6 position was substituted with an N-palmitoyl group, exhibited much higher inhibitory activity for degranulation in vitro than did 6-sPalm-AA-2G. 2-Me-6-N-Palm-AA strongly inhibit the PCA reaction in mice at lower doses than those of 6-sPalm-AA-2G. These findings suggest that 2-Me-6-N-Palm-AA may be a promising therapeutic candidate for allergic diseases.

Keywords: ascorbic acid derivatives; degranulation; passive cutaneous anaphylaxis; structure-activity relationship.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Structures of AA-2G and 6-sPalm-AA-2G.
Figure 2
Figure 2
Structures of 6-Palm-AA derivatives.
Figure 3
Figure 3
Inhibitory effects of 6-Palm-AA (a) and 6-Palm-AA derivatives (b) on antigen-induced degranulation. DNP-IgE-sensitized RBL-2H3 cells were incubated with the indicated samples and stimulated with DNP-HSA. All data represent the means ± SD of three independent cultures. * p < 0.05 and ** p < 0.01 (Dunnett’s test) as compared with the control.
Figure 4
Figure 4
Structures of 6-Palm-AA derivatives with different substituents at the C-2 or C-3 position (a) and the inhibitory effects of the 6-Palm-AA derivatives on antigen-induced degranulation (b). All data represent the means ± SD of three independent experiments. ** p < 0.01 (Dunnett’s test) as compared with the control.
Figure 5
Figure 5
Uptake quantities of 6-Palm-AA derivatives into RBL-2H3 cells (a) and the inhibitory effects of 2-Me-6-Palm-AA, 2-Me-6-N-Palm-AA, and their metabolites on antigen-induced degranulation (b). All data represent the means ± SD of three independent experiments. * p < 0.05 and ** p < 0.01 (Dunnett’s test) as compared with the control.
Figure 6
Figure 6
Inhibitory activities of 2-Me-6-Palm-AA and 2-Me-6-N-Palm-AA on calcium ionophore A23187-stimulated degranulation in RBL-2H3 cells. All data represent the means ± SD of three independent experiments. ** p < 0.01 (Dunnett’s test) as compared with the control.
Figure 7
Figure 7
Inhibitory effect of 2-Me-6-N-Palm-AA on the antigen-stimulated PCA reaction in mice. Mice were percutaneously administered the indicated samples: control (n = 9), oxatomide (n = 9), 6-sPalm-AA-2G (n = 9), 2-Me-6-Palm-AA (n = 7), and 2-Me-6-N-Palm-AA (n = 8). All data represent the means ± SE. * p < 0.05 and ** p < 0.01 (Dunnett’s test) as compared with the control. # p < 0.05 and ## p < 0.01 (t-test).
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References

    1. Wang Q., Hazeki L., Matsuhira K., Nakamura S., Yuan D., Yoshikawa M. Inhibitory effects of thunberginols A, B, and F on degranulations and releases of TNF-α and IL-4 in RBL-2H3 cells. Biol. Pharm. Bull. 2007;30:388–392. doi: 10.1248/bpb.30.388. - DOI - PubMed
    1. Nigorikawa K., Hazeki K., Guo Y., Hazeki O. Involvement of class II phosphoinositide 3-kinase α-isoform in antigen-induced degranulation in RBL-2H3 cells. PLoS ONE. 2014;9:e111698. doi: 10.1371/journal.pone.0111698. - DOI - PMC - PubMed
    1. Tajima S., Pinnell S.R. Regulation of collagen synthesis by ascorbic acid. Ascorbic acid increases type I procollagen mRNA. Biochem. Biophys. Res. Commun. 1982;106:632–637. doi: 10.1016/0006-291X(82)91157-3. - DOI - PubMed
    1. Voisin-Chiret A.S., Bazin M.-A., Lancelot J.-C., Rault S. Synthesis of new l-ascorbic ferulic acid hybrids. Molecules. 2007;12:2533–2545. doi: 10.3390/12112533. - DOI - PMC - PubMed
    1. Karbowiak T., Gougeon R.D., Alinc J.B., Brachais L., Debeaufort F., Voilley A., Chassagne D. Wine oxidation and the role of cork. Crit. Rev. Food Sci. Nutr. 2010;50:20–52. doi: 10.1080/10408390802248585. - DOI - PMC - PubMed

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