Synthesis and evaluation of novel isoxazolyl chalcones as potential anticancer agents

• Nine novel isoxazolyl chalcones were synthesized.
• They were evaluated for anticancer activity in vitro.
• Compounds bearing EWG at the 2-position in Ar group exhibited strong anticancer activities.
• Compounds 5f–i induced apoptosis by DR5 mediated extrinsic pathway in A549 cells.

A series of novel isoxazolyl chalcones were synthesized and evaluated for their activities in vitro against four types of human non-small cell lung cancer cells, including H1792, H157, A549 and Calu-1 cells. The preliminary biological screening showed that compounds 5d and 5f–i exhibited significant cytotoxicity, particularly, compounds 5f and 5h were identified as the most potent anticancer agents with IC50 values 1.35–2.07 μM and 7.27–11.07 μM against H175, A549 and Calu-1 cell lines, respectively. Compounds 5f–i could induce apoptosis in A549 cells by death receptor 5 (DR5) mediated extrinsic pathways. The preliminary structure–activity relationship study showed that compounds bearing electron withdrawing groups (EWG) at the 2-position of the phenyl ring in Ar group were more effective than those with EWG at 4-position. These results further demonstrated that the scaffolds designed in this work might lead to the discovery of novel anti-lung cancer agents.

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