Mohamed Eissa Amal Abdel Haleem, Soliman Gamal Abd El-Hakeem, Khataibeh Moayad Hussein
Pharmaceutical Chemistry Department, Faculty of Pharmacy, Cairo University, Kasr El-Aini Street, POB 11562, Cairo, Egypt.
Chem Pharm Bull (Tokyo). 2012;60(10):1290-300. doi: 10.1248/cpb.c12-00516. Epub 2012 Aug 2.
Simple, three classes of new anthranilic acid derivatives were aimed at, synthesized and tested for their toxicity, anti-inflammatory, analgesic, antipyretic activity. Also, their potential protective role against ulcerative colitis in rats was performed. Furthermore, their effect on liver and kidney functions was detected through measurement of the serum level of alanine transaminase (ALT), aspartate aminotransferase (AST), urea, creatinine and other parameters. Compounds 4, 5, 6b, 6c, 7c and 7e showed significant anti-inflammatory activity. From those 6b and 7e best improved the inflammatory indices even producing better reduction in the intensity of lesion score, ulcer area and wet weight/length ratio and showed good analgesic activity. Fortunately, none of the tested compounds showed any hepatotoxicity or nephrotoxicity. None of the tested compounds showed any antipyretic activity. Conclusively, presence of a phenyl ring in the substituent added is a must, since any alteration in its nature led to decrease in activity. Also, the presence of an extra halogen in addition to the one already embedded in the main structure was detrimental to activity.
我们针对三类简单的新型邻氨基苯甲酸衍生物进行了合成，并对其毒性、抗炎、镇痛、解热活性进行了测试。此外，还研究了它们对大鼠溃疡性结肠炎的潜在保护作用。此外，通过测量血清丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）、尿素、肌酐及其他参数，检测了它们对肝肾功能的影响。化合物4、5、6b、6c、7c和7e显示出显著的抗炎活性。其中，6b和7e能最好地改善炎症指标，甚至能更好地降低病变评分、溃疡面积和湿重/长度比的强度，并显示出良好的镇痛活性。幸运的是，所有测试化合物均未显示出任何肝毒性或肾毒性。所有测试化合物均未显示出任何解热活性。总之，在所添加的取代基中必须存在苯环，因为其性质的任何改变都会导致活性降低。此外，除了已嵌入主结构中的卤素外，额外卤素的存在对活性不利。
