Allergy‑preventive efects of linarinic acid and its tetrahydropyrrolo[2,1‑b]quinazoline derivatives isolated from Linaria vulgaris
Allergy‑preventive efects of linarinic acid and its tetrahydropyrrolo[2,1‑b]quinazoline derivatives isolated from Linaria vulgaris
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亚麻鱼中亚麻酸及其四氢吡咯并[2,1-b]喹唑啉衍生物的过敏预防作用
DOI：
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发表时间：
2018
影响因子：
3.3
通讯作者：
Hisae Oku
中科院分区：
文献类型：
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作者：
马超;Naoko Higashi;Kyoko Ishiguro;赵颖;张林魁;赵辰文;程卯生;Hisae Oku
从柳穿鱼（Linaria vulgaris Mill.）的乙醇提取物中分离得到柳穿鱼酸（Linarinicacid），即（−）-1，2，3，9-四氢吡咯并[2，1-B]喹唑啉-1-羧酸（4a）。在我们以前的研究中，合成了一系列四氢吡咯并[2，1-B]喹唑啉衍生物4 b，4c，5a，5 b，6a和6 b，它们在结构上与4a相关，并被评价为神经保护剂。本研究的目的是调查这些化合物的新功能。我们使用我们以前开发的体内测定系统检查了它们的过敏预防效果，该系统监测了用鸡蛋清溶菌酶致敏的小鼠尾静脉中血流的减少。我们观察到4a及其三个衍生物，酰胺（6a），酯（5a），溴（4 b）和醇取代基（6 b），显示出明显的过敏预防活性。本研究通过全面监测变态反应诱导期出现的特异性血流量下降，证实了四氢吡咯并[2，1-B]喹唑啉衍生物的变态反应预防活性。这一发现可能有助于开发治疗过敏性疾病如特应性皮炎、过敏性哮喘和花粉热的新药物。
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 efects using an in vivo assay system we developed previously, that monitors a decrease in blood fow 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 signifcant allergy-preventive activities. The study confrmed the allergy-preventive activity of tetrahydropyrrolo[2,1-b]quinazoline derivatives by comprehensively monitoring the specifc blood fow decrease occurring in the induction phase of allergy. This fnding may aid in the development of new agents for the treatment of allergic diseases such as atopic dermatitis, allergic asthma, and hay fever.