Design, Synthesis, Antitumor Activity and Molecular Docking Study of Novel 5-Deazaalloxazine Analogs. Academic Article uri icon


  • Protein tyrosine kinases (PTKs) are the most potential therapeutic targets for cancer. Herein, we present a sound rationale for synthesis of a series of novel 2-(methylthio), 2-(substituted alkylamino), 2-(heterocyclic substituted), 2-amino, 2,4-dioxo and 2-deoxo-5-deazaalloxazine derivatives by applying structure-based drug design (SBDD) using AutoDock 4.2. Their antitumor activities against human CCRF-HSB-2, KB, MCF-7 and HeLa have been investigated in vitro. Many 5-deazaalloxazine analogs revealed high selective activities against MCF-7 tumor cell lines (IC50: 0.17-2.17 M) over HeLa tumor cell lines (IC50 > 100 M). Protein kinase profiling revealed that compound 3h induced multi- targets kinase inhibition including -43% against (FAK), -40% against (CDKI) and -36% against (SCR). Moreover, the Annexin-V/PI apoptotic assay elucidate that compound 3h showed 33% and potentially 140% increase in early and late apoptosis to MCF-7 cells respectively, compared to the control. The structure-activity relationship (SAR) and molecular docking study using PTK as a target enzyme for the synthesized 7-deazaalloaxazine derivatives were investigated as potential antitumor agents. The AutoDock binding affinities of the 5-deazaalloxazine analogs into c-kit PTK (PDB code: 1t46) revealed reasonable correlations between their AutoDock binding free energy and IC50.

published proceedings

  • Molecules

author list (cited authors)

  • Mahmoud, S., Samaha, D., Mohamed, M. S., Abou Taleb, N. A., Elsawy, M. A., Nagamatsu, T., & Ali, H. I.

citation count

  • 3

complete list of authors

  • Mahmoud, Sawsan||Samaha, Doaa||Mohamed, Mosaad S||Abou Taleb, Nageh A||Elsawy, Mohamed A||Nagamatsu, Tomohisa||Ali, Hamed I

publication date

  • May 2020