Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt.
Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt; University of Hertfordshire Hosted by Global Academic Foundation, New Administrative Capital, Cairo, Egypt.
Bioorg Chem. 2021 Feb;107:104630. doi: 10.1016/j.bioorg.2021.104630. Epub 2021 Jan 7.
Exaggerated inflammatory responses may cause serious and debilitating diseases such as acute lung injury and rheumatoid arthritis. Two series of chalcone derivatives were prepared as anti-inflammatory agents. Methoxylated phenyl-based chalcones 2a-l and coumarin-based chalcones 3a-f were synthesized and compared for their inhibition of COX-2 enzyme and nitric oxide production suppression. Methoxylated phenyl-based chalcones showed better inhibition to COX-2 enzyme and nitric oxide suppression than the coumarin-based chalcones. Among the 18 synthesized chalcone derivatives, compound 2f exhibited the highest anti-inflammatory activity by inhibition of nitric oxide concentration in LPS-induced RAW264.7 macrophages (IC = 11.2 μM). The tested compound 2f showed suppression of iNOS and COX-2 enzymes. Moreover, compound 2f decreases in the expression of NF-κB and phosphorylated IκB in LPS-stimulated macrophages. Finally, docking studies suggested the inhibition of IKKβ as a mechanism of action and highlighted the importance of 2f hydrophobic interactions.
过度的炎症反应可能导致严重的、使人虚弱的疾病，如急性肺损伤和类风湿性关节炎。我们合成了两组查耳酮衍生物作为抗炎药物。合成了基于甲氧基苯基的查尔酮 2a-l 和香豆素基的查尔酮 3a-f，并比较了它们对 COX-2 酶的抑制作用和一氧化氮生成的抑制作用。基于甲氧基苯基的查尔酮对 COX-2 酶的抑制作用和一氧化氮的抑制作用均优于香豆素基的查尔酮。在合成的 18 种查尔酮衍生物中，化合物 2f 通过抑制 LPS 诱导的 RAW264.7 巨噬细胞中一氧化氮的浓度表现出最高的抗炎活性（IC=11.2μM）。该化合物 2f 对 iNOS 和 COX-2 酶均有抑制作用。此外，化合物 2f 降低了 LPS 刺激的巨噬细胞中 NF-κB 和磷酸化 IκB 的表达。最后，对接研究表明，抑制 IKKβ 是其作用机制，并强调了 2f 疏水性相互作用的重要性。
