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.
Research Date
Research Department
Research Journal
Chemical Biology and Drug Design
Research Publisher
Wiley online library
Research Rank
Medicinal Chemistry
Research Website
https://doi.org/10.1111/cbdd.14178
Research Year
2022
Research Member
Research_Pages
1-11
Research Abstract