某些 3-取代亚苄基氨基-2-(4-硝基苯基)喹唑啉-4(3H)-酮衍生物的合成与生物评价。

Synthesis and biological evaluation of certain 3-substituted benzylideneamino-2-(4-nitrophenyl)quinazolin-4(3H)-one derivatives.

机构信息

Department of Pharmaceutical Chemistry, College of Pharmacy, Salman bin Abdulaziz University , Al-Kharj , Saudi Arabia .

出版信息

J Enzyme Inhib Med Chem. 2015 Apr;30(2):270-6. doi: 10.3109/14756366.2014.915398. Epub 2014 Jun 18.

DOI:10.3109/14756366.2014.915398

PMID:24939093

Abstract

Certain new 3H-quinazolin-4-one Schiff's bases were synthesized and screened for their activities against ulcerative colitis "UC". Their activity against phospholipase A2 and protease enzymes was also investigated. Some compounds possessed remarkable effect with different potentials against acetic acid-induced colitis model in rats. Compound 14 (50 mg/kg) was more effective than dexamesathone (0.01 mg/kg). It produced 79.78% protection of control colitis; however, compound 13 produced 75.80% protection and was considered as effective as dexamesathone with 75.30% protection. The observed results could be explained partially by their anti-inflammatory activities which appear as phospholipase A2 (hGIIA) and/or through protease inhibitor potentials. However, all the compounds under test showed preferential inhibition towards hG-IIA type of PLA2 rather than DrG-IB with varying degrees. Interestingly, compounds 14, 13, 12 and 11 displayed excellent inhibitory activity against phospholipase A2 accompanied by protease inhibitory profile.

摘要

某些新型 3H-喹唑啉-4-酮席夫碱被合成并筛选其对溃疡性结肠炎（UC）的活性。还研究了它们对磷酸酯酶 A2 和蛋白酶的活性。一些化合物在大鼠乙酸诱导结肠炎模型中具有显著的不同潜力的作用。化合物 14（50mg/kg）比地塞米松（0.01mg/kg）更有效。它对对照结肠炎的保护率为 79.78%；然而，化合物 13 产生 75.80%的保护作用，被认为与地塞米松一样有效，保护率为 75.30%。观察到的结果可以部分解释为它们的抗炎活性，表现为磷脂酶 A2（hGIIA）和/或通过蛋白酶抑制剂潜力。然而，所有测试的化合物都显示出对 hG-IIA 型 PLA2 的优先抑制作用，而对 DrG-IB 的抑制作用则不同。有趣的是，化合物 14、13、12 和 11 对磷脂酶 A2 显示出极好的抑制活性，同时具有蛋白酶抑制谱。