Synthesis, cytotoxicity of new 4-arylidene curcumin analogues and their multi-functions in inhibition of both NF-κB and Akt signalling

A series of new 4-arylidene curcumin analogues (4-arylidene-1,7-bisarylhepta-1,6-diene-3,5-diones) were synthesized and found to be potent antiproliferative agents against a panel of cancer cell lines at submicromolar to low micromolar concentrations by SRB assay. Their inhibitory abilities against NF-κB was evaluated by High Content Analysis (HCA) based immunofluorescence assay; and the Akt signalling inhibition was determined by fluorescence polarization assay and western blot respectively. The Structure–Activity Relationship was discussed. Our results revealed that 4-arylidene curcumin analogues may work in a multi-targets manner in cancer cell.

Graphical abstractA series of new 4-arylidene curcumin analogues were found to be potent antiproliferative agents targeting both NF-κB and Akt signalling.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Twenty-six new 4-arylidene curcumin analogues were designed and synthesized. ► 4-Arylidene curcumin analogues strongly inhibit proliferation of various cancer cell lines. ► Their ability of NF-κB inhibition with SAR information was discovered. ► Selected 4-arylidene curcumin analogues inhibit Akt in low micromolar concentrations. ► Present work supported the multi-targets manner of 4-arylidene curcumin analogues.