Design, synthesis, and evaluation of the anticancer activity of 2-amino-aryl-7-aryl-benzoxazole compounds

A series of 2-amino-aryl-7-aryl-benzoxazole derivatives have been designed, synthesized, and evaluated as anticancer agents. Fourteen of the compounds exhibited cytotoxic effects toward human A549 lung cancer cells. We found 12l was the most potent with an EC₅₀ of 0.4 μm, equivalent to the anticancer drug doxorubicin, but had low selectivity following cross screening in monkey kidney Vero cells. Eight of the most potent or most selective compounds were further profiled in additional cell lines (MCF7, NCI-H187, and KB) to better understand their cytotoxic activity. Only compound 12l had a measurable EC₅₀ in a single cell line (3.3 μm in the KB cell line). Taken together, this data suggest the series as a whole display specific cytotoxicity toward A549 cells. Cheminformatics searches pointed to JAK2 as a possible target. A subset of compounds assayed at this target showed IC₅₀ s ranging from 10 to 0.08 μm; however, no clear correlation between JAK2 potency and A549 cytotoxicity was observed.