Rapid Synthesis of New DNMT Inhibitors Derivatives of Procainamide

Ludovic Halby, Christine Champion, Catherine Sénamaud-Beaufort, Sophie Ajjan, Thierry Drujon, Arumugam Rajavelu, Alexandre Ceccaldi, Renata Jurkowska, Olivier Lequin, William G. Nelson, Alain Guy, Albert Jeltsch, Dominique Guianvarc'h, Clotilde Ferroud, Paola B. Arimondo

Research output: Contribution to journalArticlepeer-review

41 Scopus citations


DNA methyltransferases (DNMTs) are responsible for DNA methylation, an epigenetic modification involved in gene regulation. Families of conjugates of procainamide, an inhibitor of DNMT1, were conceived and produced by rapid synthetic pathways. Six compounds resulted in potent inhibitors of the murine catalytic Dnmt3A/3L complex and of human DNMT1, at least 50 times greater than that of the parent compounds. The inhibitors showed selectivity for C5 DNA methyltransferases. The cytotoxicity of the inhibitors was validated on two tumour cell lines (DU145 and HCT116) and correlated with the DNMT inhibitory potency. The inhibition potency of procainamide conjugated to phthalimide through alkyl linkers depended on the length of the linker; the dodecane linker was the best.

Original languageEnglish (US)
Pages (from-to)157-165
Number of pages9
Issue number1
StatePublished - Jan 2 2012


  • Cancer
  • Conjugation
  • DNA methylation
  • Inhibitors
  • Rapid synthesis

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Organic Chemistry


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