Synthesis, Biological Evaluation and Molecular Docking Studies of Newly Synthesized 4- Amino Quinazoline Derivatives as Potential Multitarget Anticancer Agents.

Document Type : Original Article

Authors

1 Department of Medicinal Chemistry, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514, Egypt

2 Department of Medicinal Chemistry, Faculty of Pharmacy, Sinai University, Kantra, Egypt.

Abstract

A series of 4-aminoquinazoline linked to cyanopyrimidine derivatives (6a-c and 7a-f) was designed, synthesized with good yields and screened at National Cancer Institute (NCI)-disease oriented anticancer screen protocol against nine panel of cancer cell lines. Comprehensively, the structures of the synthesized compounds were confirmed by different spectroscopic methods like melting points, H1- NMR, 13C- NMR and HRMS, Moreover, the most active compound 7a was selected for in vitro enzyme inhibitory activities against epidermal growth factor receptor and cyclin dependent kinase-2 enzymes. Cell cycle analysis and apoptosis were evaluated on three different cancerous cells; UO-31, MCF-7 and IGROV-1. Finally, the molecular modelling for compound 7a inside the ATP binding site of epidermal growth factor receptor and cyclin dependent kinase-2 enzymes was performed to predict the binding mode to the active site of these enzymes using lapatinib and ribociclib as standards respectively. Our research found that quinazoline-containing cyano pyrimidine derivatives were promising cytotoxic agents for further study.

Keywords

Egyptian Journal of Chemistry
Volume 65, Issue 131 - Serial Number 13
Special Issue: Chemistry and Global Challenges (Part A)
December 2022
Pages 1121-1136

Files

History

  • Receive Date: 13 July 2022
  • Accept Date: 31 October 2022

Share

How to cite

Statistics