In this study, a series of novel substituted Ph‐1,2,3‐triazole derivatives 7(a–k) were synthesised via a combination of cycloaddition reactions, Click chemistry approach and Pd‐catalysed Suzuki–Miyaura coupling. The substituted Ph‐1,2,3‐triazoles 7(a–k) were assessed for their in vitro anti‐inflammatory activity, via in vitro experiments with Celecoxib used as the reference drug. Among the derivatives, the 4‐phenoxy‐substituted Ph‐1,2,3‐triazole (7e) (IC 50 = 14.03 ± 0.61 μM in the egg albumin denaturation method and 14.37 ± 0.76 μM in the heat‐induced haemolytic assay) and the 4‐cyano‐substituted Ph‐1,2,3‐triazole (7j) (IC 50 = 14.14 ± 0.56 μM in the egg albumin denaturation method and 14.46 ± 0.52 μM in the heat‐induced homolytic assay) exhibited excellent anti‐inflammatory activity. Attributable to the phenoxy group, acting as an electron‐donating moiety and the carbonitrile group, functioning as an electron‐withdrawing substituent, both were playing the key role to enhanced COX‐2 inhibitory activity. Furthermore, in silico molecular docking results revealed that these compounds 7(a–k) selectively inhibit COX‐2 against NADPH oxidase, exhibited strong hydrophobic interactions and hydrogen bonding, with binding affinities ranging from −8.3 to −9.1 kcal/mol.
Aitha et al. (Thu,) studied this question.