Department of Pharmaceutical Chemistry, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia.
Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt.
J Enzyme Inhib Med Chem. 2021 Dec;36(1):1067-1078. doi: 10.1080/14756366.2021.1929201.
Two series of chalcone/aryl carboximidamide hybrids and were synthesised and evaluated for their inhibitory activity against iNOS and PGE2. The most potent derivatives were further checked for their anti-inflammatory activity utilising carrageenan-induced rat paw oedema model. Compounds , , and were proved to be the most effective inhibitors of PGE2, LPS-induced NO production, iNOS activity. Moreover, , , and showed significant oedema inhibition ranging from 62.21% to 78.51%, compared to indomethacin (56.27 ± 2.14%) and celecoxib (12.32%). Additionally, , and displayed good COX2 inhibitory activity while , and exhibited the highest 5LOX inhibitory activity. Compounds , , and fit nicely into the pocket of iNOS protein (PDB ID: 1r35) the important amino acid residues. Prediction of physicochemical parameters exhibited that , , and had acceptable physicochemical parameters and drug-likeness. The results indicated that chalcone/aryl carboximidamides , , and , in particular and , could be used as promising lead candidates as potent anti-inflammatory agents.
合成了两个系列的查尔酮/芳基碳酰亚胺杂合体 和 ，并评估了它们对 iNOS 和 PGE2 的抑制活性。最有效的衍生物进一步利用角叉菜胶诱导的大鼠足肿胀模型检查其抗炎活性。证明化合物 、 、 和 是 PGE2、LPS 诱导的 NO 产生、iNOS 活性的最有效抑制剂。此外，与吲哚美辛（56.27 ± 2.14%）和塞来昔布（12.32%）相比， 、 、 和 对水肿的抑制作用显著，范围为 62.21%至 78.51%。此外， 、 、 对 COX2 具有良好的抑制活性，而 、 、 对 5LOX 具有最高的抑制活性。化合物 、 、 和 很好地适合 iNOS 蛋白（PDB ID：1r35）的口袋，与重要的氨基酸残基结合。物理化学参数的预测表明， 、 、 和 具有可接受的物理化学参数和类药性。结果表明，查尔酮/芳基碳酰亚胺杂合体 、 、 和 ，特别是 和 ，可用作有前途的先导候选物，作为有效的抗炎剂。
