Neal T M, Winterbourn C C, Vissers M C
Biochem Pharmacol. 1987 Sep 1;36(17):2765-8. doi: 10.1016/0006-2952(87)90262-0.
Sulfasalazine is a potent inhibitor of superoxide production and granule enzyme release by stimulated neutrophils, and modulation of these responses may contribute to its anti-inflammatory properties. It is a composite drug consisting of 5-aminosalicylic acid and sulfapyridine joined through an azo linkage. To investigate which functional groups on the molecule are active against neutrophil responses, 5-aminosalicylic acid, sulfapyridine and olsalazine were added to cells stimulated with fMet-Leu-Phe or immune complexes. The inhibitory effects of sulfasalazine on superoxide production, degranulation and neutrophil-mediated collagen degradation were closely mimicked by olsalazine, with the other two compounds having little effect on either function. Thus the azo link appears to be the important structural feature of sulfasalazine that affects neutrophil responses. This suggests that sulfasalazine could be anti-inflammatory in its own right rather than just acting as a source of 5-aminosalicylic acid. Our findings are also a favourable indication for olsalazine (Dipentum), which is currently under trial as an anti-inflammatory agent.
柳氮磺胺吡啶是刺激的中性粒细胞超氧化物生成和颗粒酶释放的有效抑制剂，这些反应的调节可能有助于其抗炎特性。它是一种由5-氨基水杨酸和磺胺吡啶通过偶氮键连接而成的复合药物。为了研究分子上哪些官能团对中性粒细胞反应有活性，将5-氨基水杨酸、磺胺吡啶和奥沙拉嗪添加到用甲酰甲硫氨酸-亮氨酸-苯丙氨酸或免疫复合物刺激的细胞中。奥沙拉嗪紧密模拟了柳氮磺胺吡啶对超氧化物生成、脱颗粒和中性粒细胞介导的胶原蛋白降解的抑制作用，而其他两种化合物对这两种功能几乎没有影响。因此，偶氮键似乎是柳氮磺胺吡啶影响中性粒细胞反应的重要结构特征。这表明柳氮磺胺吡啶本身可能具有抗炎作用，而不仅仅是作为5-氨基水杨酸的来源。我们的发现对目前正在作为抗炎剂进行试验的奥沙拉嗪（得舒特）也是一个有利的迹象。
