Synthesis, in vitro cytotoxicity and apoptosis inducing study of 2-aryl-3-nitro-2H-chromene derivatives as potent anti-breast cancer agents

• Compounds 4a–u were designed as new cytotoxic and apoptosis inducing agents.
• Compounds 4a–u were synthesized from β-nitrostyrenes and salicylaldehydes.
• The cytotoxicity of compounds 4a–u was tested against breast cancer cell lines.
• Most of the tested compounds were more potent than standard drug etoposide.
• Selected compounds 4h and 4l induce apoptosis via the activation of caspase-3.

A series of 2-aryl-3-nitro-2H-chromenes 4a–u were designed as hybrid analogs of flavanone, β-nitrostyrene and nitrovinylstilbene scaffolds. They were synthesized from the reaction of appropriate β-nitrostyrenes and salicylaldehydes in good yields. In vitro cytotoxic activities of compounds 4a–u were tested against breast cancer cell lines including MCF-7, T-47D and MDA-MB-231. Most compounds exhibited good cytotoxic activity against selected cell lines, being more potent than standard drug etoposide. Representatively, 8-methoxy-3-nitro-2-(4-chlorophenyl)-2H-chromene (4l) with IC50 = 0.2 μM against MCF-7 cells, was 36-times more potent than etoposide. Apoptosis as a mechanism of cell death for selected compounds 4h and 4l was confirmed morphologically by acridine orange/ethidium bromide double staining and TUNEL analysis, as well as caspase-3 activation assay.

A series of 2-aryl-3-nitro-2H-chromenes 4a–u were designed and synthesized as hybrid analogs of β-nitrostyrene, nitrovinylstilbene and flavanone scaffolds with apoptosis-inducing cytotoxic activity against breast cancer cells.Figure optionsDownload as PowerPoint slide