Lead compound bearing caffeic scaffold induces EGFR suppression in solid tumor cancer cells

A small molecule egfr inhibitor,4-(2-(3-(4-(4-(trifluoromethyl)phenyl)thiazol-2-yl)ureido)vinyl)-1,2-phenylene diacetate (ciu1) was designed in silico by using caffeic scaffold as core structure. the designed compound showed anti-proliferative action against different solid tumor cell lines,particularly metastatic breast cancer cells. ciu1 inhibited the growth of egfr-overexpressing mda-mb-468 triple-negative breast cancer cells and wild-type non-small-cell lung cancer h460 cells with ic50 values of 8.96 μm and 12.98 μm,respectively,these anti-proliferative effects of ciu1 were comparable to gefitinib (a specific egfr inhibitor) or lapatinib (a dual egfr and her2 tyrosine kinase inhibitor). interestingly ciu1 effectively inhibited the invasive hormone-dependent mcf-7 cancer cells with an ic50 2.34 μm. the immunoblot analyses revealed that ciu1 induced programmed cell death and suppressed egfr expression in egfr-overexpressing breast cancer (mda-mb468) and lung cancer (pc-9) cells. the findings substantiated our design strategy and demonstrated the potential of ciu1 as new lead for further optimization in the development of anticancer drugs against advanced solid tumors. © 2015 faculty of health and social studies,university of south bohemia in ceske budejovice. published by elsevier sp. z o.o. all rights reserved.