Naproxen Based 1,3,4-Oxadiazole Derivatives as EGFR Inhibitors: Design, Synthesis, Anticancer, and Computational Studies.
Mohammad Mahboob AlamSyed NazreenAbdulraheem S A AlmalkiAhmed A ElhenawyNawaf I AlsenaniSerag Eldin I ElbehairiAzizah M MalebariMohammad Y AlfaifiMeshari A AlsharifSulaiman Y M AlfaifiPublished in: Pharmaceuticals (Basel, Switzerland) (2021)
A library of novel naproxen based 1,3,4-oxadiazole derivatives (8-16 and 19-26) has been synthesized and screened for cytotoxicity as EGFR inhibitors. Among the synthesized hybrids, compound2-(4-((5-((S)-1-(2-methoxynaphthalen-6-yl)ethyl)-1,3,4-oxadiazol-2-ylthio)methyl)-1H-1,2,3-triazol-1-yl)phenol(15) was the most potent compound against MCF-7 and HepG2cancer cells with IC50 of 2.13 and 1.63 µg/mL, respectively, and was equipotent to doxorubicin (IC50 1.62 µg/mL) towards HepG2. Furthermore, compound 15 inhibited EGFR kinase with IC50 0.41 μM compared to standard drug Erlotinib (IC50 0.30 μM). The active compound induces a high percentage of necrosis towards MCF-7, HePG2 and HCT 116 cells. The docking studies, DFT and MEP also supported the biological data. These results demonstrated that these synthesized naproxen hybrids have EGFR inhibition effects and can be used as leads for cancer therapy.
Keyphrases
- epidermal growth factor receptor
- small cell lung cancer
- tyrosine kinase
- cancer therapy
- advanced non small cell lung cancer
- drug delivery
- cell cycle arrest
- induced apoptosis
- breast cancer cells
- molecular dynamics
- emergency department
- ionic liquid
- density functional theory
- cell proliferation
- small molecule
- endoplasmic reticulum stress
- protein kinase
- protein protein