Skip to main content
 

 

 

EGFR and COX-2 Dual Inhibitor: The Design, Synthesis, and Biological Evaluation of Novel Chalcones

Author name : AbdElAziz Ahmed H Nayl
Publication Date : 2022-03-05
Journal Name : molecules

Abstract

For most researchers, discovering new anticancer drugs to avoid the adverse effects of current ones, to improve therapeutic benefits and to reduce resistance is essential. Because the COX-2 enzyme plays an important role in various types of cancer leading to malignancy enhancement, inhibition of apoptosis, and tumor-cell metastasis, an indispensable objective is to design new scaffolds or drugs that possess combined action or dual effect, such as kinase and COX-2 inhibition. The start compounds A1 to A6 were prepared through the diazo coupling of 3-aminoacetophenone with a corresponding phenol and then condensed with two new chalcone series, C7–18. The newly synthesized compounds were assessed against both COX-2 and epidermal growth factor receptor (EGFR) for their inhibitory effect. All novel compounds were screened for cytotoxicity against five cancer cell lines. Compounds C9 and G10 exhibited potent EGFR inhibition with IC50 values of 0.8 and 1.1 µM, respectively. Additionally, they also displayed great COX-2 inhibition with IC50 values of 1.27 and 1.88 µM, respectively. Furthermore, the target compounds were assessed for their cytotoxicity against pancreatic ductal cancer (Panc-1), lung cancer (H-460), human colon cancer (HT-29), human malignant melanoma (A375) and pancreatic cancer (PaCa-2) cell lines. Interestingly, compounds C10 and G12 exhibited the strongest cytotoxic effect against PaCa-2 with average IC50 values of 0.9 and 0.8 µM, respectively. To understand the possible binding modes of the compounds under investigation with the receptor cites of EGFR and COX-2, a virtual docking study was conducted.

Keywords

EGFR; COX-2; kinase; anticancer; anti-inflammatory

Publication Link

https://doi.org/10.3390/ molecules27041158

Block_researches_list_suggestions

Suggestions to read

Photocurrent and electrical properties of SiGe Nanocrystals grown on insulator via Solid-state dewetting of Ge/SOI for Photodetection and Solar cells Applications
MOHAMMED OMAR MOHAMMEDAHMED IBRAHIM
Comparative analysis of high-performance UF membranes with sulfonated polyaniline: Improving hydrophilicity and antifouling capabilities for water purification
EBTSAM KHALEFAH H ALENEZY
Efficient framework for energy management of microgrid installed in Aljouf region considering renewable energy and electric vehicles
Ali fathy mohmmed ahmed
Comparative analysis of high-performance UF membranes with sulfonated polyaniline: Improving hydrophilicity and antifouling capabilities for water purification
AHMED HAMAD FARHAN ALANAZI
Contact