Abstract

A new series of quinazolinone compounds 1634 incorporating isatin moieties was synthesized. The antitumor efficacy of the compounds against MDA-MB-231, a breast cancer cell line, and LOVO, a colon cancer cell line, was assessed. Compounds 20, 21, 22, 23, 25, 27, 28, 29, 30, 31, 32, 33, and 34 displayed potent antitumor activity against MDA-MB-231 and LOVO cells (IC50: 10.38–38.67 μM and 9.91–15.77 μM, respectively); the comparative IC50 values for 5-fluorouracil and erlotinib in these cells lines were 70.28 μM, 22.24 μM and 15.23 μM, 25.31 μM respectively. The EGFR-TK assay and induction of apoptosis for compound 31 were investigated to assess its potential cytotoxic activity as a representative example of the novel synthesized compounds. At a concentration of 10 μM, compound 31 exhibited efficient inhibitory effect against EGFR-TK and induced apoptosis in MDA-MB-231 cells. Furthermore, a molecular docking study for compound 31 and erlotinib was performed to verify the binding mode toward the EGFR kinase enzyme, and showed a similar interaction as that with erlotinib alone.

Graphical Abstract: Compound 31 showed potent antitumor activity and efficient inhibitory effect against EGFR-TK and induced apoptosis of MDA-MB-231 cells at a concentration of 10 μM.

Details

Title
Synthesis, anticancer and apoptosis-inducing activities of quinazoline–isatin conjugates: epidermal growth factor receptor-tyrosine kinase assay and molecular docking studies
Author
El-Azab, Adel S 1 ; Al-Dhfyan, Abdullah 2 ; Abdel-Aziz, Alaa A-M 3 ; Abou-Zeid, Laila A 4 ; Alkahtani, Hamad M 5 ; Al-Obaid, Abdulrahman M 5 ; Al-Gendy, Manal A 5 

 Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia;; Department of Organic Chemistry, Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt; 
 Stem Cell & Tissue Reengineering Program, King Faisal Specialized Hospital and Research Center, Riyadh, Saudi Arabia;; Department of Pharmacology & Toxicology, Collage of Pharmacy, King Saud University, Riyadh, Saudi Arabia; 
 Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia;; Department of Medicinal Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt; 
 Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt 
 Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia; 
End page
944
Publication year
2017
Publication date
Dec 2017
Publisher
Taylor & Francis Ltd.
ISSN
14756366
e-ISSN
14756374
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2195229016
Copyright
© 2017 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. This work is licensed under the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.