Potent inhibitory activity of hydroxylated 2-benzylidene-3,4-dihydronaphthalen-1(2H)-ones on LPS-stimulated reactive oxygen species production in RAW 264.7 macrophages
- Bioorg Med Chem Lett. 2022 Oct 1:73:128921. doi: 10.1016/j.bmcl.2022.128921.
- 1. College of Pharmacy, Yeungnam University, Gyeongsan 38541, Republic of Korea.
- 2. College of Pharmacy, University of Kentucky, Lexington, KY 40536, USA.
- 3. College of Pharmacy, Yeungnam University, Gyeongsan 38541, Republic of Korea. Electronic address: [email protected].
- 4. College of Pharmacy, Yeungnam University, Gyeongsan 38541, Republic of Korea. Electronic address: [email protected].
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.