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Breast cancer is a disease in which cells in the breast divide continuously without control. There are great limitations in cancer chemotherapy. Hence, it is essential to search for new cancer therapeutics. Herein, a novel series of EGFR/HER2 dual inhibitors has been designed based on the hybridization of thiazole and pyrazoline fragments. The synthesized compounds were screened for their anti-proliferative activity against MCF-7 breast cancer cell line and MCF-10 normal breast cell line. Interestingly, synthesized compounds <b>6e</b> and <b>6k</b> showed very potent antiproliferative activity towards MCF-7 with IC₅₀ values of 7.21 and 8.02 µM, respectively. Furthermore, enzymatic assay was performed against EGFR and HER2 to prove the dual inhibitory action. Compounds <b>6e</b> and <b>6k</b> showed potent inhibitory activity for EGFR with IC₅₀ of 0.009 and 0.051 µM, respectively, and for HER2 with IC₅₀ of 0.013 and 0.027 µM, respectively. Additionally, compounds <b>6e</b> and <b>6k</b> significantly stimulated apoptotic breast cancer cell death. Compound <b>6e</b> was further explored for its anticancer activity in vivo using a Xenograft model. Moreover, computational modeling studies, ADMET studies and toxicity prediction were performed to investigate their potential drug candidates.