Scoparone chemical modification into semi-synthetic analogues featuring 3-substitution for their anti-inflammatory activity

Natural products (NPs) continue to serve as a structural model for the development of new bioactive molecules and improve the process of identifying novel medicines. The biological effects of coumarins, one of the most researched compounds among NPs, are currently being thoroughly investigated. In the present investigation, we reported the synthesis of nineteen semi-synthetic 3-substituted scoparone analogues, followed by their characterization using analytical methods such as NMR, HPLC, and HRMS. All compounds screened for in vitro and in vivo study for their ability to reduce inflammation. The SAR study worked effectively for this particular scoparone 3-substitution, as compounds 3, 4, 9, 16, 18, and 20 displayed improved in vitro results for TNF-α than the parent molecule. Similarly, compounds 3, and 17 showed a higher percentage of IL-6 inhibition. Compounds 3, 4, and 12 have also been identified by in vivo studies as promising candidates with higher percent inhibition than the parent scoparone molecule. As evident from all in vitro and in vivo studies, compound 3 showed the most potent anti-inflammatory activity among all. [Figure not available: see fulltext.]