Design, synthesis, and anti-inflammatory activity studies of indanone derivatives containing cinnamic acid skeleton.

Reactive oxygen species (ROS), as small-molecule signaling intermediates, are geynthesis and activity of aurone and indanone derivatinerated by immune and somatic cells in response to damage, infection, or stimulation. During the inflammatory response, ROS participate in the activation of the NF-κB pathway, leading to the upregulation of pro-inflammatory cytokines. Inflammatory mediators serve as key regulatory and effector molecules that initiate, amplify, and coordinate the inflammatory process and contribute to the resolution of inflammation at later stages. Against this backdrop, 1-indanone is a small-molecule scaffold with anti-inflammatory potential that is present in natural products and can exert its effect by inhibiting the production of ROS. To explore this potential further, 18 novel 1-indanone derivatives were designed based on the natural cinnamic acid scaffold. Their anti-inflammatory activities were evaluated using cellular models. After the assessment of cytotoxicity and ROS scavenging capacity, three compounds (6a, 6l, and 6o) were selected for further analysis. Subsequent measurement of inflammatory markers, including nitric oxide (NO), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6), revealed that compounds 6a and 6o exhibited the most potent anti-inflammatory activities. Moreover, molecular docking studies demonstrated that these two compounds possessed strong binding affinities for TAK1. These findings highlighted the therapeutic potential of 1-indanone derivatives in modulating inflammation and suggested that compounds 6a and 6o warrant further preclinical investigation.