Asymmetrical 2,6-bis(benzylidene)cyclohexanones: Synthesis, cytotoxic activity and QSAR study

In order to develop novel anti-cancer agents, a series of asymmetrical 2,6-bis (benzylidene)cyclohexanone derivatives containing nitrobenzylidene moiety were synthesized and their cytotoxic activity were determined in vitro against MDA-MB 231, MCF-7 and SK-N-MC cell lines using MTT assay. Among the tested compounds, the highest activity against MDA-MB 231 cells was achieved by 2-(3-bromo-5-methoxy-4-propoxybenzylidene)-6-(2-nitrobenzylidene)cyclohexanone (compound 5d). Whereas, compound 5j (the 3-nitro analog of compound 5d) was the most potent compound against MCF-7 and SK-N-MC cell lines. The results indicated that the cytotoxic activity profile against different tumor cells can be optimized by desired 4-alkoxy-3-bromo-5-methoxybenzylidene scaffold.

A series of asymmetrical 2,6-bis(benzylidene)cyclohexanones were synthesized as cytotoxic agents. The highest activity against MCF-7 and SK-N-MC cells was achieved by compound 5j (IC50 ≤ 1.51 μg/ml).Figure optionsDownload as PowerPoint slideHighlights
► A series of asymmetrical 2,6-bis(benzylidene)cyclohexanones were synthesized.
► The cytotoxic activity of compounds was assessed using MTT method.
► The highest activity against MCF-7 and SK-N-MC cells was achieved by compound 5j.
► The activity was optimized by desired 4-alkoxy-3-bromo-5-methoxybenzylidene group.