Synthesis and anticancer activity of novel spiro-isoxazoline and spiro-isoxazolidine derivatives of α-santonin

In the present study, novel spiro derivatives of α-santonin were prepared and tested for their anticancer activity against a panel of six human cancer cell lines. Spiro-isoxazoline and spiro-isoxazolidine derivatives have been generated on C-ring of α-santonin (α-methylene-γ-butyrolactone) by the 1,3-dipolar cycloaddition of α-santonin derivative 6 with nitrile oxides 7 and nitrones 9 respectively. Among all, compound 10b″ had shown IC50 of 0.01, 0.5 and 0.3 μM against PC-3, THP-1 and MCF-7 cell lines respectively. Further, flow cytometry studies showed that PC-3 cells treated with the spiro-isoxazolidine derivative 10b″ were arrested in the sub G1 phase of the cell cycle in a concentration dependent manner. The spiro-isoxazolidine derivative 10b″ also showed concentration dependent inhibitory activity against NF-κB, p65 with 57% inhibition in 24 h at 10 μM.

Graphical abstractNovel spiro derivatives of α-santonin have been generated and tested in vitro for their anticancer activity. Few compounds demonstrated potent cytotoxicity and were found to be the inhibitor of NF-κB.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Novel spiro-isoxozoline and spiro-isoxazolidine derivatives of α-santonin synthesised. ► Some of the compounds demonstrated potent anticancer activity. ► Novel spiro-derivatives of α-santonin were found to be the inhibitor of NF-κB.