Caffeine-hydrazones as anticancer agents with pronounced selectivity toward T-lymphoblastic leukaemia cells

Bioorg Chem. 2015 Jun:60:19-29. doi: 10.1016/j.bioorg.2015.03.003. Epub 2015 Apr 2.

Abstract

We report design and synthesis of set of novel anticancer agents based on caffeine-hydrazones bearing 2-hydroxyaryl- or 2-N-heteroaryl moiety. Anticancer activity evaluation using seven cancer cell lines and two non-malignant cell lines demonstrated that several derivatives display significant anticancer activity and great selectivity index toward T-lymphoblastic leukaemia cells. In general, hydrazones bearing 2-N-heteroaryl moiety are more active and selective than those with 2-hydroxyaryl moiety. Tested compounds exhibit dose-dependent inhibition of both RNA and DNA synthesis, with some exceptions. Antimicrobial activities were tested on set of twelve bacterial and yeast strains, however prepared compounds were not active, suggesting for a molecular target specific for eukaryotic cells.

Keywords: Anticancer agents; Caffeine–hydrazones; Cancer treatment; Leukaemia; Selectivity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Infective Agents / chemistry
  • Anti-Infective Agents / pharmacology
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Bacteria / drug effects
  • Caffeine / chemistry*
  • Caffeine / pharmacology*
  • Cell Line
  • Cell Line, Tumor
  • Fungi / drug effects
  • Humans
  • Hydrazones / chemistry*
  • Hydrazones / pharmacology*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
  • Structure-Activity Relationship

Substances

  • Anti-Infective Agents
  • Antineoplastic Agents
  • Hydrazones
  • Caffeine