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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

مؤلف البحث
Mohamed T.- E.Maghraby | Ola I. A. Salem | Bahaa G. M. Youssif | Mahmoud M. Sheha
تاريخ البحث
مجلة البحث
Chemical Biology and Drug Design
الناشر
Wiley online library
تصنيف البحث
Medicinal Chemistry
موقع البحث
https://doi.org/10.1111/cbdd.14178
سنة البحث
2022
صفحات البحث
1-11
ملخص البحث

A novel series of 1,2,3-triazole/chalcone hybrids 6a– n was designed and synthe-
sized 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 doxoru-
bicin (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 (IC 50 = 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 interac-
tions with the EGFR-TK domain for the inhibitors. In cell cycle analysis, hybrid
6d caused a cell cycle arrest at the G1 transition phase.