This study attempted to discover tetralone-derived potent ROS inhibitors by synthesizing sixty-six hydroxylated and halogenated 2-benzylidene-3,4-dihydronaphthalen-1(2H)-ones via Claisen-Schmidt condensation reaction. The majority of the synthesized and investigated compounds significantly inhibited ROS in LPS-stimulated RAW 264.7 macrophages. When compared to malvidin (IC₅₀ = 9.00 µM), compound 28 (IC₅₀ = 0.18 µM) possessing 6-hydroxyl and 2-trifluoromethylphenyl moiety showed the most potent ROS inhibition. In addition, the compounds 20, 31, 39, 45, 47-48, 52, 55-56, 58-60, and 62 also displayed ten folds greater ROS inhibitory activity relative to the reference compound. Based on the structure-activity relationship study, incorporating hydroxyl groups at the 6- and 7-positions of tetralone scaffold along with different halogen functionalities in phenyl ring B is crucial for potent ROS suppression. This study contributes to a better understanding of the effect of halogen and phenolic groups in ROS suppression, and further investigations on 2-benzylidene-3,4-dihydronaphthalen-1(2H)-ones will potentially lead to the discovery of effective anti-inflammatory agents.

本研究试图通过 Claisen-Schmidt缩合反应合成 66 个羟基化和卤化的 2-亚苄基-3,4-二氢萘-1(2 H )-酮来发现四氢萘酮衍生的强效 ROS 抑制剂。大多数合成和研究的化合物显着抑制 LPS 刺激的 RAW 264.7 巨噬细胞中的 ROS。与锦葵素 (IC ₅₀ = 9.00 µM) 相比，具有 6-羟基和 2-三氟甲基苯基部分的化合物28 (IC _{50 = 0.18 µM) 显示出最有效的 ROS 抑制作用。}此外，化合物20、31、39、45、47- _ _ _ _ _ _ _与参考化合物相比，图48、52、55-56、58-60和62也显示出高十倍的ROS抑制活性。基于构效关系研究，在四氢萘酮支架的 6 位和 7 位结合羟基以及苯环 B 中的不同卤素官能团对于有效的 ROS 抑制至关重要。本研究有助于更好地了解卤素和酚基在 ROS 抑制中的作用，对 2-benzylidene-3,4-dihydronaphthalen-1(2 H )-ones 的进一步研究可能会导致发现有效的抗炎症剂。