An Integrative Informatics Approach to Explain the Mechanism of Action of N1-(Anthraquinon-2-yl) Amidrazones as BCR/ABL Inhibitors

Dima A. Sabbah, Rima Hajjo, Kamal Sweidan, Haizhen A. Zhong

Research output: Contribution to journalArticlepeer-review


Background: Drugs incorporating heterocyclic chemical skeletons possess a plethora of therapeutic activities such as anticancer, antimicrobial, antihypertensive, and antipsychiatric effects. It is becoming routine, nowadays, to use cheminformatics and bioinformatics methods to elucidate the mechanism(s) of action of such drugs. Objective: This study aimed to probe the activity of a recently published series of N1-(anthraquinon-2-yl) amidrazone piperazine derivatives employing computational strategies[1], identify their structural basis of binding to BCR/ABL kinase domain, and explain their anticancer activities in human breast adenocarcinoma (MCF-7) and chronic myelogenous leukemia (K562) cell lines. Methods: We applied an in silico integrative informatics approach integrating molecular descriptors, docking studies, cheminformatics, and network analysis. Results: Our results highlighted the possible involvement of the BCR/ABL and DRD2 pathways in the anticancer activity of the studied compounds, and induced fit docking (IFD) indicated that the BCR/ABL kinase domain is a putative drug target. Additionally, high-scoring docking poses identified a unique network of hydrogen bonding with amino acids Y253, K271, E286, V299, L301, T315, M318, I360, R362, V379, and D3810. Conclusion: Using an integrative informatics approach to characterize our anticancer compounds, we were able to explain the biological differences between synthesized and biologically validated amidrazone piperazine anticancer agents. We were also able to postulate a mechanism of action of this novel group of anticancer agents.

Original languageEnglish (US)
Pages (from-to)817-830
Number of pages14
JournalCurrent Computer-Aided Drug Design
Issue number6
StatePublished - Oct 2021


  • Chemical-protein interactions
  • Cheminformatics
  • DRD2
  • IFD
  • K562
  • MCF-7
  • Molecular descriptors
  • N1-(Anthraquinon-2-yl) Amidrazones
  • Network analysis
  • Similarity searching

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery


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