Photo-inducible cytotoxic and clastogenic activities of 3,6-di-substituted acridines obtained by acylation of proflavine

Eur J Med Chem. 2009 Jun;44(6):2459-67. doi: 10.1016/j.ejmech.2009.01.010. Epub 2009 Jan 20.


The cytotoxicity and photo-enhanced cytotoxicity of a series of 18 3,6-di-substituted acridines were evaluated on both tumour CHO cells and human normal keratinocytes, and compared to their corresponding clastogenicity as assessed by the micronucleus assay. Compounds 2f tert-butyl N-[(6-tert-butoxycarbonylamino)acridin-3-yl]carbamate and 2d N-[6-(pivalamino)acridin-3-yl]pivalamide displayed a specific cytotoxicity on CHO cells. These results suggested that the two derivatives could be considered as interesting candidates for anticancer chemotherapy and hypothesized that the presence of 1,1-dimethylethyl substituents was responsible for a strong nonclastogenic cytotoxicity. Compounds 2b and 2c, on the contrary, displayed a strong clastogenicity. They indicated that the presence of nonbranched aliphatic chains on positions 3 and 6 of the acridine rings tended to induce a significant clastogenic effect. Finally, they established that most of the acridine compounds could be photo-activated by UVA-visible rays and focussed on the significant role of light irradiation on their biological properties.

MeSH terms

  • Acridines / chemistry
  • Acridines / pharmacology*
  • Acridines / radiation effects*
  • Acylation
  • Animals
  • CHO Cells
  • Cell Proliferation / drug effects
  • Cricetinae
  • Cricetulus
  • Drug Evaluation, Preclinical
  • Humans
  • Keratinocytes / drug effects*
  • Light*
  • Micronucleus Tests
  • Molecular Structure
  • Photochemistry
  • Proflavine / chemistry*
  • Stereoisomerism
  • Structure-Activity Relationship


  • Acridines
  • Proflavine