Structure–activity relationships of hybrid annonaceous acetogenins: Powerful growth inhibitory effects of their connecting groups between heterocycle and hydrophobic carbon chain bearing THF ring on human cancer cell lines

Five novel hybrid molecules of annonaceous acetogenins and insecticides targeting mitochondrial complex I were synthesized and their growth inhibitory activities against 39 human cancer cell lines were investigated. It was revealed that the connecting group between the N-methylpyrazole part and the hydrophobic alkyl chain bearing the THF ring influenced their biological activities significantly. Amide-connected analog 2, in particular, showed selective and very potent activity (<10 nM) against some cancer cell lines.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Five hybrid molecules of annonaceous acetogenins and insecticides were synthesized. ► Growth inhibitory activities against 39 human cancer cell lines were investigated. ► Amide-connected analog showed potent activity against specific cancer cell lines. ► Connecting group between two pharmacophores influenced biological activity.