Home|Journals Follow on Twitter| Subscribe to List

Directory for Medical Articles

Open Access

Original Research

Dihydrofolate reductase (DHFR) inhibition and molecular modeling study of some 6-bromo- or 6,8-dibromo-quinazolin-4(3H)-ones

Abdelfattah A. Abdelkhalek, Heba A. Ewida, Shahenda M. El-Messery, Hossam S. A. Mahmoud, Ashraf F. Wasfy, Esraa A. M. Moharram, Hussein I. El-Subbagh.

Objectives: The dihydrofolate reductase (DHFR) inhibitory activity of 6-bromo- and 6,8-dibromo-quinazolin-4(3H)-ones (725) were studied to define the structural features and requirements that enhance selectivity and specificity for the proper binding to the enzyme active site. Methods: Compounds 725 were tested for their in vitro DHFR inhibition. As an appli - cation of the use of DHFR inhibitors, in vitro antitumor activity using disease-oriented human cell lines assay was performed. Key findings: Compounds 19, 20, and 22 showed remarkable DHFR inhibitory activity, inhibitory concentration (IC 50 0.6, 0.2, and 0.1 μM, respectively). Compounds 12, 17, 18, 20, and 24 proved to be broad spectrum antitumor with median IC 50 values of 0.6, 0.6, 0.5, 0.6, and 0.7 μM, respectively. Molecular docking study results revealed that the active DHFR inhibitors 22 and 20 bind to DHFR with similar amino acid residues as methotrexate, especially Arg 28. Conclusions: The mono-bromo series proved to be more active than the di-bromo coun - terparts and the 3-(2-hydrazinyl-acetyl)- is more active than its 3-(acetohydrazide) isoster. The investigated compounds could be used as template model for further optimization.

Key words: Quinazolines, DHFR inhibition, antitumor screening, molecular modeling study

Share this Article

American Journal of Diagnostic Imaging


ScopeMed Home
Follow ScopeMed on Twitter
Author Tools
eJPort Journal Hosting
About ScopeMed
License Information
Terms & Conditions
Privacy Policy
Contact Us

The articles in Scopemed are open access articles licensed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License (https://creativecommons.org/licenses/by-nc-sa/4.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.
ScopeMed is a Database Service for Scientific Publications. Copyright ScopeMed Information Services.
Scopemed Buttons