Abdel-Aziz Mohamed, Beshr Eman A, Abdel-Rahman Islam M, Ozadali Keriman, Tan Oya Unsal, Aly Omar M
Medicinal Chemistry Department, Faculty of Pharmacy, Minia University, Minia 61519, Egypt.
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Hacettepe University, 06100 Sihhiye, Ankara, Turkey.
Eur J Med Chem. 2014 Apr 22;77:155-65. doi: 10.1016/j.ejmech.2014.03.001. Epub 2014 Mar 3.
A series of novel 1-(4-methoxyphenyl)-5-(3,4,5-trimethoxyphenyl)-1H-1,2,4-triazole-3-carboxamides were synthesized and confirmed with different spectroscopic techniques. The prepared compounds exhibited remarkable anti-inflammatory activity that represents 38%-100% of indomethacin activity and 44%-115% of celecoxib activity after 3 h. The anilides 5a-l and hydrazide 6 exhibit low incidence of gastric ulceration compared to indomethacin which was confirmed with histopathological investigation. In vitro COX-1/COX-2 inhibition studies showed compounds 4b (COX-1 IC50 = 45.9 μM; COX-2 IC50 = 68.2 μM) and 6 (COX-1 IC50 = 39.8 μM; COX-2 IC50 = 46.3 μM) are the most potent COX inhibitors in the tested compounds. The binding mode for some of the tested compounds to the enzymes was predicted using docking studies.
合成了一系列新型的1-(4-甲氧基苯基)-5-(3,4,5-三甲氧基苯基)-1H-1,2,4-三唑-3-甲酰胺，并采用不同的光谱技术进行了确证。所制备的化合物表现出显著的抗炎活性，在3小时后，其活性相当于吲哚美辛活性的38%-100%以及塞来昔布活性的44%-115%。与吲哚美辛相比，苯胺类化合物5a-l和酰肼6表现出较低的胃溃疡发生率，这一点通过组织病理学研究得到了证实。体外COX-1/COX-2抑制研究表明，化合物4b（COX-1 IC50 = 45.9 μM；COX-2 IC50 = 68.2 μM）和6（COX-1 IC50 = 39.8 μM；COX-2 IC50 = 46.3 μM）是测试化合物中最有效的COX抑制剂。使用对接研究预测了一些测试化合物与酶的结合模式。
