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Design,synthesis, and modelling study of new 1,2,3-triazole/chalcone hybrids with antiproliferative action as epidermal growth factor receptor inhibitors |
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| Authors: | Mohamed T-E Maghraby Ola I A Salem Bahaa G M Youssif Mahmoud M Sheha |
| Institution: | 1. Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Assiut University, Assiut, Egypt
Pharmaceutical Chemistry Department, Faculty of Pharmacy, New Valley University, Egypt;2. Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Assiut University, Assiut, Egypt;3. Department of Medicinal Chemistry, Faculty of Pharmacy, Assiut University, Assiut, Egypt Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Sphinx University, Assiut, Egypt |
| 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 (IC50 values 0.95–1.80 μM) compared to doxorubicin (IC50 1.14 μM). The most potent antiproliferative derivative, compound 6d , was also the most potent EGFR inhibitor with an IC50 of 0.09 ± 0.05 μM, which is comparable to the reference Erlotinib (IC50 = 0.05 ± 0.03 μM). 6d has modest BRAF inhibitory action with an IC50 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. |
| Keywords: | 1 2 3-triazole anticancer cell cycle EGFR viability |