Synthesis of dehydroabietic acid derivatives as mast cell stabilizers

Mast cell degranulation plays a central role in IgE-driven allergic diseases, yet the therapeutic options for stabilizers remain limited. Rosinane diterpenoids, a class of natural polyphenols known for their anti-inflammatory properties, represent an attractive source for novel anti-allergic compounds. Dehydroabietic acid (DHAA), a member of this class, exhibits diverse biological activities, yet its potential in mast cell regulation remains unexplored. In this study, we designed and synthesized a series of novel DHAA derivatives. We evaluated their anti-allergic effects in IgE/antigen-stimulated bone marrow-derived mast cells (BMMCs), and found that compound 4f significantly and dose-dependently inhibited IgE-mediated Ca²⁺ influx and suppressed mast cell degranulation. Moreover, in vivo studies demonstrated that compound 4f effectively attenuated passive cutaneous anaphylaxis in mice and reduced vascular leakage. These findings indicate that compound 4f represents a novel mast cell stabilizer and provides a promising structural scaffold for developing new anti-allergic therapeutics.