Allergy-preventive effects of linarinic acid and its tetrahydropyrrolo[2,1-b]quinazoline derivatives isolated from Linaria vulgaris.

Linarinic acid, (-)-1,2,3,9-tetrahydropyrrolo[2,1-b]quinazoline-1-carboxylic acid (4a), was isolated from the ethanol extract of Linaria vulgaris Mill. In our previous study, a series of tetrahydropyrrolo[2,1-b]quinazoline derivatives 4b, 4c, 5a, 5b, 6a and 6b that were structurally related to 4a and evaluated as neuroprotective agents were synthesized. The aim of the present study was to investigate the novel features of these compounds. We examined their allergy-preventive effects using an in vivo assay system we developed previously, that monitors a decrease in blood flow in the tail vein of mice subjected to sensitization with hen egg-white lysozyme. We observed that 4a and its three derivatives, amide (6a), ester (5a), bromine (4b), and alcohol substituent (6b), showed significant allergy-preventive activities. The study confirmed the allergy-preventive activity of tetrahydropyrrolo[2,1-b]quinazoline derivatives by comprehensively monitoring the specific blood flow decrease occurring in the induction phase of allergy. This finding may aid in the development of new agents for the treatment of allergic diseases such as atopic dermatitis, allergic asthma, and hay fever.