Design, Synthesis and Evaluation of the Anti-Cancer Activity of 2-Amino-aryl-7-aryl-benzoxazole Compounds

Abstract

A series of 2-aminoaryl-7-arylbenzoxazole derivatives have been designed, synthesized and evaluated as anti-cancer agents. Fourteen of the compounds exhibited cytotoxic effects towards Human A549 lung cancer cells. We found 12l was the most potent with an EC₅₀ of 0.4 μM, equivalent to the anti-cancer 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 suggests the series as a whole display specific cytotoxicity towards A549 cells. Cheminformatics searches pointed to JAK2 as a possible target. A subset of compounds assayed at this target showed IC₅₀s ranging from 10 μM to 0.08 μM, however no clear correlation between JAK potency and A549 cytotoxicity was observed.

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The SAR expansion of 2-aminoaryl-7-arylbenzoxazole hits obtained from screening in A549 cells is reported. New compounds with improved physical properties have been prepared which have micromolar cytotoxic activity against the A549 cell-line

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