ABSTRACT Sclareol is well‐documented for its potent anti‐inflammatory properties, making it a promising candidate for chronic inflammatory disorders; however, it is toxic to normal cells. In order to address this, we have successfully synthesized a new series of arylated derivatives of sclareol via the Heck reaction. Among all the synthesized compounds, SCL‐1 showed 92.81% viability at 20 uM, which is far better than the parent molecule. Further, synthesized compounds were evaluated for the first time for their anti‐inflammatory potential. Based on cell viability assays, SCL‐1 was further investigated in a lipopolysaccharide (LPS)‐induced nitric oxide (NO) release assay in RAW 264.7 macrophages. Here, SCL‐1 exhibited 38.39% inhibition, better than the parent molecule sclareol, which demonstrated 26.44% inhibition at 5 µM. These results suggest that SCL‐1 exerts superior NO suppressive activity compared to the parent molecule. Given its significant NO inhibitory effect, SCL‐1 was further assessed for its impact on pro‐inflammatory cytokines. At a concentration of 20 µM, SCL‐1 significantly inhibited TNF‐α and IL‐6 by 52.32% and 53.58%, respectively. Moreover, SCL‐1 effectively mitigated LPS‐induced oxidative stress, reducing reactive oxygen species (ROS) production by 47.69% at the same concentration. In silico and Swiss‐ADMET studies of SCL‐1 showed significant potential as a lead for the development of novel anti‐inflammatory agents.
Sharma et al. (Sat,) studied this question.