National Research Centre, Pharmaceutical and Drug Industries Research Division, Dokki-Giza 12622, Egypt.
Department of Medicinal Chemistry, College of Pharmacy, University of Sharjah, Sharjah 27272, United Arab Emirates.
Molecules. 2021 Oct 27;26(21):6489. doi: 10.3390/molecules26216489.
A series of thirteen triarylpyrazole analogs were investigated as inhibitors of lipopolysaccharide (LPS)-induced prostaglandin E (PGE) and nitric oxide (NO) production in RAW 264.7 macrophages. The target compounds - have first been assessed for cytotoxicity against RAW 264.7 macrophages to determine their non-cytotoxic concentration(s) for anti-inflammatory testing to make sure that the inhibition of PGE and NO production would not be caused by cytotoxicity. It was found that compounds and were the most potent PGE inhibitors with IC values of 7.1 and 1.1 μM, respectively. In addition, these compounds also showed inhibitory effects of 11.6% and 37.19% on LPS-induced NO production, respectively. The western blots analysis of COX-2 and iNOS showed that the PGE and NO inhibitory effect of compound are attributed to inhibition of COX-2 and iNOS protein expression through inactivation of p38.
我们研究了一系列十三元三芳基吡唑类似物，以评估它们对 RAW 264.7 巨噬细胞中脂多糖 (LPS) 诱导的前列腺素 E (PGE) 和一氧化氮 (NO) 产生的抑制作用。这些靶化合物首先被评估对 RAW 264.7 巨噬细胞的细胞毒性，以确定其用于抗炎测试的非细胞毒性浓度，以确保 PGE 和 NO 产生的抑制作用不是由细胞毒性引起的。结果发现，化合物 和 是最有效的 PGE 抑制剂，IC 值分别为 7.1 和 1.1 μM。此外，这些化合物对 LPS 诱导的 NO 产生的抑制作用分别为 11.6%和 37.19%。COX-2 和 iNOS 的 Western blot 分析表明，化合物 的 PGE 和 NO 抑制作用归因于通过失活 p38 抑制 COX-2 和 iNOS 蛋白表达。
