Synthetic Approaches and Biological Evaluation of Novel Coumarin Based Compounds

Abstract

Coumarins, which are 2H-1-benzopiran-2-one compounds originating from some plants, have been proven to be anticancer, antibacterial, and anticancer agents. Around of these structures are currently accepted for the treatment of cardiovascular disease (warfarin), antibiotics (novobiocin or chlorobiocin), and anticancer medications (geiparvarin). We created 38 coumarin derivatives (2–50), 22 of which were novel, in this project by replacing the eighth carbon of the benzopiran ring with nearly aromatic and aliphatically substituted piperidine and piperazines. This was done because of the structure's great potential and the dearth of research on molecules resulting from the benzopiranone heterocycle. The produced compounds' cytotoxicity, analgesic, and anti-inflammatory qualities were evaluated. The targeted molecules were made in two steps. Using the Pechmann reaction, the 7-hydroxy-4-methyl-chromen-2-one coumarin scaffold was created in the first step. Another phase was the derivatization of the 7-hydroxy-4-methyl-chromen-2-one coumarin scaffold (compound 1) by addition of piperidine and aromatic and aliphatic substituted piperazine groups.

In vitro tests were used to evaluate the cytotoxicity, analgesic, and anti-inflammatory properties. MTT assay was employed to assess the cytotoxicity of MCF-7 breast cancer cells and RAW264.7 macrophages. The nitrite inhibition test was employed to evaluate anti-inflammatory activity using RAW264.7 macrophage cells. The reference drugs for the cytotoxicity and anti-inflammatory tests were L-NAME and indomethacin (IND). PGE2 production for the painkilling effect was noted. The outcomes indicated that compounds 11, 23, and 31 have promising anti-inflammatory activity. Compound 11 produced better results than the reference drugs and were three times more active than IND. Moreover, compound 11 confirmed little cytotoxicity and a moderate analgesic effect.