Costantino L, Parenti C, Di Bella M, Zanoli P, Baraldi M
Cattedra di Chimica Farmaceutica e Tossicologica, Università di Modena, Italy.
Pharmacol Res. 1993 May-Jun;27(4):349-58. doi: 10.1006/phrs.1993.1034.
Four new 2,6-bis-(1,1-dimethylethyl)phenol derivatives were synthesized and evaluated for their anti-inflammatory activity, in comparison with indomethacin and vitamin E, using the carrageenan paw oedema assay in rats. Among the tested compounds, the 4-(6,7-dichloro-4H-1,2,4-benzothiadiazine-3-yl)-2,6-bis-(1,1- dimethylethyl)-phenol-S,S-dioxide (4) was the most active compound markedly reducing oedema formation. Moreover compound 4 potentiated, particularly in the early phase of carrageenan paw swelling (2-4 h), the antiphlogistic effect of indomethacin. This compound, on the other hand, did not show ulcerogenic activity at therapeutic doses and did not potentiate the gastric damage induced by high doses of indomethacin. In vitro, the studied compounds (1-4) showed to be moderately active as scavengers of 2,2-diphenyl-1-(2,4,6-trinitrophenyl)hydrazil, 4 being the most active among them. Compound 4, on the contrary, was practically inactive on liposome peroxidation where compounds 1, 2, 3, which are modest anti-inflammatory agents, exerted a good or moderate effect.
合成了四种新型2,6 - 双（1,1 - 二甲基乙基）苯酚衍生物，并与吲哚美辛和维生素E相比，通过角叉菜胶致大鼠足爪水肿试验评估了它们的抗炎活性。在所测试的化合物中，4 - （6,7 - 二氯 - 4H - 1,2,4 - 苯并噻二嗪 - 3 - 基）-2,6 - 双（1,1 - 二甲基乙基）苯酚 - S，S - 二氧化物（4）是活性最强的化合物，能显著减轻水肿形成。此外，化合物4尤其在角叉菜胶致足爪肿胀的早期阶段（2 - 4小时）增强了吲哚美辛的抗炎作用。另一方面，该化合物在治疗剂量下未表现出致溃疡活性，也未增强高剂量吲哚美辛诱导的胃损伤。在体外，所研究的化合物（1 - 4）作为2,2 - 二苯基 - 1 - （2,4,6 - 三硝基苯基）肼自由基清除剂显示出中等活性，其中化合物4活性最强。相反，化合物4对脂质体过氧化几乎无活性，而作为适度抗炎剂的化合物1、2、3则发挥了良好或中等的作用。
