Abd-Ellah Heba S, Abdel-Aziz Mohamed, Shoman Mai E, Beshr Eman A M, Kaoud TamerS, Ahmed Al-Shaimaa F F
Medicinal Chemistry Department, Faculty of Pharmacy, Minia University, Minia 61519, Egypt.
Medicinal Chemistry Department, Faculty of Pharmacy, Minia University, Minia 61519, Egypt.
Bioorg Chem. 2017 Oct;74:15-29. doi: 10.1016/j.bioorg.2017.06.003. Epub 2017 Jun 15.
A series of new 1,3,4-oxadiazole/oxime hybrids were synthesized and designed as potent COX inhibitors. The prepared compounds were evaluated for their anti-inflammatory, antioxidant and ulcerogenic activities. The results indicated that the prepared compounds exhibited remarkable anti-inflammatory activity with (69.60-109.60% of indomethacin activity) after 4h. In vitro COX inhibitory assay showed that compounds 6d and 7h are potent COX inhibitors with IC of (1.10-0.94) and (2.30-5.00) µM on both COX-1 and COX-2 respectively. Compound 7h was found to inhibit both COXs non-competitively with K values of 73µM and 89µM. Most of the tested compounds showed ulcer-free stomachs compared to indomethacin.
合成了一系列新型1,3,4-恶二唑/肟杂化物，并将其设计为有效的COX抑制剂。对所制备的化合物进行了抗炎、抗氧化和致溃疡活性评估。结果表明，所制备的化合物在4小时后表现出显著的抗炎活性（相当于消炎痛活性的69.60 - 109.60%）。体外COX抑制试验表明，化合物6d和7h是有效的COX抑制剂，对COX-1和COX-2的IC50分别为(1.10 - 0.94)和(2.30 - 5.00) μM。发现化合物7h以非竞争性方式抑制两种COX，K值分别为73μM和89μM。与消炎痛相比，大多数测试化合物的胃均未出现溃疡。
