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

• Caffeine–hydrazones were prepared in three-step synthesis.
• Anticancer activity tested on the 7 cancer and 2 healthy cell lines.
• High activity and great selectivity towards T-lymphoblastic leukaemia cells.
• Antimicrobial activity tested on 13 bacterial stains, compounds were not active.
• Binding properties towards biologically important metal ions.

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.

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