Synthesis, characterization, biological evaluation and molecular docking of a new quinazolinone-based derivative as a potent dual inhibitor for VEGFR-2 and EGFR tyrosine kinases

Yassine Riadi; Mubarak A Alamri; Mohammed H Geesi; El Hassane Anouar; Oussama Ouerghi; Alhumaidi B Alabbas; Manal A Alossaimi; Ali Altharawi; Oussama Dehbi; Safar M Alqahtani

doi:10.1080/07391102.2021.1890221

Synthesis, characterization, biological evaluation and molecular docking of a new quinazolinone-based derivative as a potent dual inhibitor for VEGFR-2 and EGFR tyrosine kinases

J Biomol Struct Dyn. 2022 Sep;40(15):6810-6816. doi: 10.1080/07391102.2021.1890221. Epub 2021 Mar 8.

Authors

Affiliations

¹ Department of Pharmaceutical Chemistry, College of Pharmacy, Prince Sattam bin Abdulaziz University, Al-Kharj, Saudi Arabia.
² Department of Chemistry, College of Science and Humanities in Al-Kharj, Prince Sattam bin Abdulaziz University, Al-Kharj, Saudi Arabia.
³ Department of Physic, College of Science and Humanities in Al-Kharj, Prince Sattam bin Abdulaziz University, Al-Kharj, Saudi Arabia.
⁴ Université Tunis El Manar, Tunis, Tunisia.
⁵ Department of Chemistry, College of Science and Arts of Al Qurayyat, Jouf University, Saudi Arabia.

PMID: 33682611
DOI: 10.1080/07391102.2021.1890221

Abstract

An efficient process for the preparation of a new ethyl 2-((3-(4-fluorophenyl)-6-methyl-4-oxo-3,4-dihydroquinazolin-2-yl)thio) acetate (5) was described. The prepared derivative was synthesized using the S-arylation method. Several analytical techniques, such as NMR, Raman and infrared spectroscopy, were used to characterize this compound. The compound was screened for cytotoxic activity against three human cancer cell lines: human cervical cancer (HeLa), human lung adenocarcinoma (A549) and triple negative breast cancer (MDA-MB-231) cells using an MTT assay. It exhibited potent cytotoxic activity against the tested cell lines with IC₅₀ values in the low micromolar range when compared to a standard drug, docetaxel. It also displayed potent inhibitory activity towards VEGFR-2 and EGFR tyrosine kinases, reflecting its potential to act as an effective anti-cancer agent.Communicated by Ramaswamy H. Sarma.

Keywords: MD simulation; Quinazolinone; S-arylation; docking; tyrosine kinase.

MeSH terms

Antineoplastic Agents* / chemistry
Cell Line, Tumor
Cell Proliferation
Drug Design
Drug Screening Assays, Antitumor
ErbB Receptors / metabolism
Humans
Molecular Docking Simulation
Molecular Structure
Protein Kinase Inhibitors / chemistry
Protein Kinase Inhibitors / pharmacology
Quinazolinones / pharmacology
Structure-Activity Relationship
Tyrosine
Vascular Endothelial Growth Factor Receptor-2* / metabolism
Vascular Endothelial Growth Factor Receptor-2* / pharmacology

Substances

Antineoplastic Agents
Protein Kinase Inhibitors
Quinazolinones
Tyrosine
EGFR protein, human
ErbB Receptors
KDR protein, human
Vascular Endothelial Growth Factor Receptor-2