Methylenedioxy flavonoids: Assessment of cytotoxic and anti-cancer potential in human leukemia cells

• Synthesis of a chalcone with a mono methoxy group at the ortho position in A-ring.
• Significant effect on down-regulation proliferation and viability of leukemia cells.
• Induction of apoptotic cell death.
• Cytotoxic effect is cell type-specific and targets preferentially cancer cells.

A new series of chalcones, flavanones and flavones with methylenedioxy group at the 3ʹ,4ʹ position in chalcone, 7,8 position in flavanones and flavones with mono-, di- and trimethoxy groups in the benzaldehyde ring have been assessed for their effect on proliferation, cytotoxic potential and apoptosis in human leukemia cells. Among the tested compounds, the chalcone series showed the best activity and chalcone 3 (mono methoxy group at the ortho position in A-ring) showed a significant effect on down-regulation of cancer cell proliferation and viability in three different leukemia cell lines (K562, Jurkat, U937). The executioner caspase cleavage analyses indicated that the cytotoxic effect mediated by chalcone 3 is due to induction of apoptotic cell death. Interestingly, the cytotoxic effect was cell type-specific and targeted preferentially cancer cells as peripheral blood mononuclear cells (PBMCs) from healthy donors were less affected by the treatment compared to K562, Jurkat and U937 leukemia cells. Altogether our results indicate a potential drug candidate with interesting differential toxicity obeying Lipinski's rule of five.

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