Design, synthesis, and modelling study of new 1,2,3‐triazole/chalcone hybrids with antiproliferative action as epidermal growth factor receptor inhibitors
Mohamed T.‐E. Maghraby, Ola I. A. Salem, Bahaa G. M. Youssif, Mahmoud Sheha
Abstract
Abstract A novel series of 1,2,3‐triazole/chalcone hybrids 6a–n was designed and synthesized using a molecular hybridization approach to develop a new cytotoxic agent capable of targeting epidermal growth factor receptor (EGFR) and/or BRAF. The antiproliferative effect of the novel hybrids was investigated against four cancer cells using doxorubicin as a reference. Hybrids 6a , 6d , 6f–h , and 6n have the highest antiproliferative activity (IC 50 values 0.95–1.80 μM) compared to doxorubicin (IC 50 1.14 μM). The most potent antiproliferative derivative, compound 6d , was also the most potent EGFR inhibitor with an IC 50 of 0.09 ± 0.05 μM, which is comparable to the reference Erlotinib (IC 50 = 0.05 ± 0.03 μM). 6d has modest BRAF inhibitory action with an IC 50 of 0.90 ± 0.10 μM. The findings were also related to molecular docking studies, which provided models of strong interactions with the EGFR‐TK domain for the inhibitors. In cell cycle analysis, hybrid 6d caused a cell cycle arrest at the G1 transition phase.