Expedient synthesis and anticancer evaluation of dual-action 9-anilinoacridine methyl triazene chimeras

Dipak Walunj, Katarina Egarmina, Helena Tuchinsky, Ofer Shpilberg, Oshrat Hershkovitz-Rokah, Flavio Grynszpan, Gary Gellerman

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


The efficient synthesis of molecular hybrids including a DNA-intercalating 9-anilinoacridine (9-AnA) core and a methyl triazene DNA-methylating moiety is described. Nucleophilic aromatic substitution (SNAr) and electrophilic aromatic substitution (EAS) reactions using readily accessible starting materials provide a quick entry to novel bifunctional anticancer molecules. The chimeras were evaluated for their anticancer activity. Chimera 7b presented the highest antitumor activity at low micromolar IC50 values in antiproliferative assays performed with various cancer cell lines. In comparison, compound 7b outperformed DNA-intercalating drugs like amsacrine and AHMA. Mechanistic studies of chimera 7b suggest a dual mechanism of action: methylation of the DNA-repairing protein MGMT associated with the triazene structural portion and Topo II inhibition by intercalation of the acridine core.

Original languageEnglish
Pages (from-to)237-252
Number of pages16
JournalChemical Biology and Drug Design
Issue number2
StatePublished - Feb 2021


  • Anilinoacridine
  • Anticancer
  • EAS
  • Molecular chimera
  • SAr
  • Triazene


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