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

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

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.

MeSH terms

  • Animals
  • Anti-Allergic Agents* / chemical synthesis
  • Anti-Allergic Agents* / chemistry
  • Anti-Allergic Agents* / pharmacology
  • Ascorbic Acid* / analogs & derivatives
  • Ascorbic Acid* / chemical synthesis
  • Ascorbic Acid* / chemistry
  • Ascorbic Acid* / pharmacology
  • Cell Degranulation / drug effects*
  • Disease Models, Animal
  • Hypersensitivity / drug therapy*
  • Mice
  • Passive Cutaneous Anaphylaxis*

Substances

  • Anti-Allergic Agents
  • Ascorbic Acid