Synthesis and antileishmanial activity of 6-mono-substituted and 3,6-di-substituted acridines obtained by acylation of proflavine

Eur J Med Chem. 2007 Oct;42(10):1277-84. doi: 10.1016/j.ejmech.2007.02.010. Epub 2007 Mar 1.

Abstract

Two new series of diaminoacridinic derivatives obtained from proflavine and N-(6-amino-3-acridinyl)acetamide were synthesised and assessed for their cytotoxic and antileishmanial activities. Two compounds, N-[6-(acetylamino)-3-acridinyl]acetamide and N-[6-(benzoylamino)-3-acridinyl]benzamide demonstrated highly specific antileishmanial properties against the intracellular amastigote form of the parasite. Structure-activity relationships established that the antiproliferative activity against human cells was greatly enhanced by the presence of a benzoylamino group in 6-mono-substituted acridines, while the presence of two acetylamino or benzoylamino groups in 3,6-di-substituted acridines strongly increased the specificity of the molecules for Leishmania parasite, suggesting that symmetric conformations could preferentially interfere with Leishmania metabolism.

MeSH terms

  • Acridines / chemical synthesis
  • Acridines / chemistry*
  • Acridines / toxicity*
  • Acylation
  • Animals
  • Antiprotozoal Agents / chemical synthesis*
  • Antiprotozoal Agents / chemistry
  • Antiprotozoal Agents / toxicity*
  • Leishmania infantum / drug effects*
  • Molecular Structure
  • Proflavine / chemistry*

Substances

  • Acridines
  • Antiprotozoal Agents
  • Proflavine