Antiallergic Activity of 6-Deoxy-2-<i>O</i>-methyl-6-(<i>N</i>-hexadecanoyl)amino-<span style="font-variant: small-caps">l</span>-ascorbic Acid
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-<...
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MDPI AG
2021-08-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/26/15/4684 |
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| author | Kaori Miura Hiroaki Matsuno Yuji Iwaoka Hideyuki Ito Akihiro Tai |
| author_facet | Kaori Miura Hiroaki Matsuno Yuji Iwaoka Hideyuki Ito Akihiro Tai |
| author_sort | Kaori Miura |
| collection | DOAJ |
| description | 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-<i>O</i>-α-<span style="font-variant: small-caps;">d</span>-glucopyranosyl-6-<i>O</i>-hexadecanoyl-<span style="font-variant: small-caps;">l</span>-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-<i>O</i>-methyl-6-(<i>N</i>-hexadecanoyl)amino-<span style="font-variant: small-caps;">l</span>-ascorbic acid (2-Me-6-<i>N</i>-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 <i>N</i>-palmitoyl group, exhibited much higher inhibitory activity for degranulation in vitro than did 6-sPalm-AA-2G. 2-Me-6-<i>N</i>-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-<i>N</i>-Palm-AA may be a promising therapeutic candidate for allergic diseases. |
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| language | English |
| last_indexed | 2024-03-10T09:11:23Z |
| publishDate | 2021-08-01 |
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| series | Molecules |
| spelling | doaj.art-b8a9626d4e04433ab3042eb3cd7cbb7e2023-11-22T06:01:48ZengMDPI AGMolecules1420-30492021-08-012615468410.3390/molecules26154684Antiallergic Activity of 6-Deoxy-2-<i>O</i>-methyl-6-(<i>N</i>-hexadecanoyl)amino-<span style="font-variant: small-caps">l</span>-ascorbic AcidKaori Miura0Hiroaki Matsuno1Yuji Iwaoka2Hideyuki Ito3Akihiro Tai4LAIMU Corporation, 3-6-12 Shinyokohama, Kohoku-ku, Yokohama, Kanagawa 222-0033, JapanFaculty of Life and Environmental Sciences, Prefectural University of Hiroshima, 5562 Nanatsuka-cho, Shobara, Hiroshima 727-0023, JapanFaculty of Health and Welfare Science, Okayama Prefectural University, 111 Kuboki, Soja, Okayama 719-1197, JapanFaculty of Health and Welfare Science, Okayama Prefectural University, 111 Kuboki, Soja, Okayama 719-1197, JapanFaculty of Life and Environmental Sciences, Prefectural University of Hiroshima, 5562 Nanatsuka-cho, Shobara, Hiroshima 727-0023, JapanAllergy 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-<i>O</i>-α-<span style="font-variant: small-caps;">d</span>-glucopyranosyl-6-<i>O</i>-hexadecanoyl-<span style="font-variant: small-caps;">l</span>-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-<i>O</i>-methyl-6-(<i>N</i>-hexadecanoyl)amino-<span style="font-variant: small-caps;">l</span>-ascorbic acid (2-Me-6-<i>N</i>-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 <i>N</i>-palmitoyl group, exhibited much higher inhibitory activity for degranulation in vitro than did 6-sPalm-AA-2G. 2-Me-6-<i>N</i>-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-<i>N</i>-Palm-AA may be a promising therapeutic candidate for allergic diseases.https://www.mdpi.com/1420-3049/26/15/4684ascorbic acid derivativesdegranulationpassive cutaneous anaphylaxisstructure-activity relationship |
| spellingShingle | Kaori Miura Hiroaki Matsuno Yuji Iwaoka Hideyuki Ito Akihiro Tai Antiallergic Activity of 6-Deoxy-2-<i>O</i>-methyl-6-(<i>N</i>-hexadecanoyl)amino-<span style="font-variant: small-caps">l</span>-ascorbic Acid Molecules ascorbic acid derivatives degranulation passive cutaneous anaphylaxis structure-activity relationship |
| title | Antiallergic Activity of 6-Deoxy-2-<i>O</i>-methyl-6-(<i>N</i>-hexadecanoyl)amino-<span style="font-variant: small-caps">l</span>-ascorbic Acid |
| title_full | Antiallergic Activity of 6-Deoxy-2-<i>O</i>-methyl-6-(<i>N</i>-hexadecanoyl)amino-<span style="font-variant: small-caps">l</span>-ascorbic Acid |
| title_fullStr | Antiallergic Activity of 6-Deoxy-2-<i>O</i>-methyl-6-(<i>N</i>-hexadecanoyl)amino-<span style="font-variant: small-caps">l</span>-ascorbic Acid |
| title_full_unstemmed | Antiallergic Activity of 6-Deoxy-2-<i>O</i>-methyl-6-(<i>N</i>-hexadecanoyl)amino-<span style="font-variant: small-caps">l</span>-ascorbic Acid |
| title_short | Antiallergic Activity of 6-Deoxy-2-<i>O</i>-methyl-6-(<i>N</i>-hexadecanoyl)amino-<span style="font-variant: small-caps">l</span>-ascorbic Acid |
| title_sort | antiallergic activity of 6 deoxy 2 i o i methyl 6 i n i hexadecanoyl amino span style font variant small caps l span ascorbic acid |
| topic | ascorbic acid derivatives degranulation passive cutaneous anaphylaxis structure-activity relationship |
| url | https://www.mdpi.com/1420-3049/26/15/4684 |
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