LAIMU Corporation, 3-6-12 Shinyokohama, Kohoku-ku, Yokohama, Kanagawa 222-0033, Japan.
Faculty of Life and Environmental Sciences, Prefectural University of Hiroshima, 5562 Nanatsuka-cho, Shobara, Hiroshima 727-0023, Japan.
Molecules. 2021 Aug 3;26(15):4684. doi: 10.3390/molecules26154684.
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--α-d-glucopyranosyl-6--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--methyl-6-(-hexadecanoyl)amino-l-ascorbic acid (2-Me-6--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 -palmitoyl group, exhibited much higher inhibitory activity for degranulation in vitro than did 6-sPalm-AA-2G. 2-Me-6--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--Palm-AA may be a promising therapeutic candidate for allergic diseases.
过敏是一种对特定抗原的过度免疫反应。I 型过敏,如花粉热和食物过敏,近年来显著增加,已成为全球性问题。我们之前报道过,一种具有棕榈酰基和葡萄糖基的抗坏血酸衍生物,2--α-d-吡喃葡萄糖基-6--十六烷酰基-l-抗坏血酸(6-sPalm-AA-2G),在体外显示出抑制脱粒的作用,并在小鼠被动皮肤过敏反应(PCA)反应中显示出抑制作用。在这项研究中,合成了几种抗坏血酸的棕榈酸衍生物,并进行了构效关系研究,以发现具有更强脱粒抑制活性的更有效的抗坏血酸衍生物。6-脱氧-2--甲基-6-(-十六烷酰基)氨基-l-抗坏血酸(2-Me-6--Palm-AA),其中在抗坏血酸 C-2 位的羟基上引入了一个甲基,并且在 C-6 位的羟基被棕榈酰基取代,在体外显示出比 6-sPalm-AA-2G 更高的脱粒抑制活性。2-Me-6--Palm-AA 在较低剂量下比 6-sPalm-AA-2G 更强烈地抑制小鼠的 PCA 反应。这些发现表明 2-Me-6--Palm-AA 可能是治疗过敏疾病的有前途的候选药物。