Convenient route to benzo[1,2,3]selenadiazole-isoxazole hybrids and evaluation of their in vitro cytotoxicity

A series of novel benzo[1,2,3]selenadiazole-isoxazole hybrid compounds were designed and synthesized from natural (R)-carvone. These derivatives were synthesized from the selenation reaction between the corresponding semicarbazones and selenium dioxide (SeO2) in the presence of glacial acetic acid as a solvent. The structures of the newly synthesized products were fully characterized by spectroscopic analysis (H-1, C-13 NMR) and HRMS. All the synthesized compounds were tested in vitro against four human cancer cell lines, fibrosarcoma (HT-1080), lung (A-549) and breast (MCF-7 and MDA-MB-231) carcinoma to evaluate their anticancer activity. Most of the semicarbazones and some of the benzo[1,2,3]selenadiazole-isoxazole hybrids showed interesting cell growth inhibitory activity with IC50 values ranging from 10 to 20 mu M. Furthermore, semicarbazone bearing 3-phenylisoxazole nucleus and the benzo[1,2,3]selenadiazole-3-p-chlorophenylisoxazole hybrid exhibited significant antiproliferative activity against HT-1080 cells with IC50 values close to 10.9 +/- 1.2 and 18.6 +/- 2.6 mu M, respectively. Furthermore, the semicarbazone bearing a phenyl group on C3 position of the isoxazole nucleus and the 3-(4-chlorophenyl)-benzo[1,2,3]selenadiazole-isoxazole hybrid had a quite good survival performance against MRC5 cells. The mechanism of action of this latter suggested that it induces apoptosis through caspase-3/7 activation.

Automated summary

A series of novel benzo[1,2,3]selenadiazole-isoxazole hybrid compounds were synthesized from natural (R)-carvone. These compounds showed promising anticancer activities and may serve as potential anticancer agents.