5 years ago

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

Design, synthesis, and evaluation of the anticancer activity of 2-amino-aryl-7-aryl-benzoxazole compounds
Kiattawee Choowongkomon, Siriruk Rattanabunyong, Patcharaporn Khajondetchairit, Praphasri Suphakun, Matthew Paul Gleeson, Oraphan Phuangsawai
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 IC50s ranging from 10 to 0.08 μm; however, no clear correlation between JAK2 potency and A549 cytotoxicity was observed. The SAR expansion of 2-amino-aryl-7-aryl-benzoxazole 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.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1111/cbdd.13025

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