Gold(I)-Catalyzed Synthesis of 4<i>H</i>-Benzo[<i>d</i>][1,3]oxazines and Biological Evaluation of Activity in Breast Cancer Cells

Abstract

The first gold(I)-catalyzed cycloisomerization procedure applied to the synthesis of substituted 4<i>H</i>-benzo[<i>d</i>][1,3]oxazines has been developed starting from <i>N</i>-(2-alkynyl)aryl benzamides. The chemoselective oxygen cyclization via the 6-<i>exo</i>-dig pathway yielded the observed heterocycles in modest to good chemical yields under very mild reaction conditions. The obtained oxazines were assayed on the breast cancer (BC)-derived cell lines MCF-7 and HCC1954 with differential biological activity. The newly synthesized 4<i>H</i>-benzo[<i>d</i>][1,3]oxazine compounds showed several degrees of cell proliferation inhibition with a remarkable effect for those compounds having a substituted aryl at C-2 of the molecules. The 4<i>H</i>-benzo[<i>d</i>][1,3]oxazines showed an IC₅₀ ranking from 3.1 to 95 μM in MCF-7 and HCC1954 cells. These compounds represent potential drug candidates for BC treatment. However, additional assays are needed to elucidate their complete effect over the cellular and molecular hallmarks of cancer.