A New Sorafenib Isoster and its Rearrangement Product: Synthesis, Characterization, and in Vitro Cytotoxicity and Enzyme Inhibition Studies

Abstract Cancer is a devastating disease, with female breast cancer becoming the leading cause of global cancer morbidity. Sorafenib is a multiple kinase inhibitor, and exhibits activity against a wide spectrum of tumor types, however, in some cases it proves insufficient. Synthesis of sorafenib analogs can be an efficient way to discover potent cancer therapeutic agents. In this work, we intended to design sorafenib analogs and determine their antiproliferative activity against five cancer cell lines (A549, HepG2, HCT116, MDA‐MB‐231, and PC‐3) using MTS method. As a result, we synthesized a sorafenib analog 1 A and its base‐promoted arranged compound 1 A2 . Their in‐vitro cytotoxicity and potencies in the epidermal growth factor receptor (EGFR) inhibition study revealed that compound 1 A displayed higher inhibition activity than cisplatin in MDA‐MB‐231 (breast cancer) cells with an IC 50 value of 16.18±1.42 μ M. The structure of 1 A2 was explicitly confirmed by the single‐crystal X‐ray diffraction analysis.