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

The first gold(I)-catalyzed cycloisomerization procedure applied to the synthesis of substituted 4H-benzo[d][1,3]-oxazines has been developed starting from N-(2-alkynyl)aryl benzamides. The chemoselective oxygen cyclization via the 6-exo-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 4H-benzo[d][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 4H-benzo[d][1,3]oxazines showed an IC50 ranking from 3.1 to 95 mu M 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.

Automated summary

A gold(I)-catalyzed cycloisomerization procedure was developed for the synthesis of substituted 4H-benzo[d][1,3]-oxazines. The obtained compounds showed potential as drug candidates for breast cancer treatment.