Biological evaluation of new mimetics of annonaceous acetogenins: Alteration of right scaffold by click linkage with aromatic functionalities

•A convergent fragment-assembly approach was developed.•A small library of annonaceous acetogenin analogues was established.•Lots of aromatic moieties were introduced using Click chemistry.•Biological evaluation of annonaceous acetogenin analogues was studied.

A small library of analogues of annonaceous acetogenins through click linkage with aromatic moieties is established using a convergent modular fragment-assembly approach. These analogues exhibited low micromolar inhibitory activities against the proliferation of several human cancer cell lines. Structure–activity relationship (SAR) of these analogues indicates that replacement of the methoxy groups of ubiquinone ring with methyl groups is proved to be a useful strategy for improving the anticancer activity of quinone–acetogenin hybrids.

Graphical abstractA variety of aromatic moieties were introduced for the first time into the right part of acetogenins, in which a triazole functionality was employed as the linkage using Click chemistry. Figure optionsDownload full-size imageDownload as PowerPoint slide