Unveiling the Relationship between Structure and Anticancer Properties of Permethylated Anigopreissin A: A Study with Thirteen Analogues

Abstract

Permethylated anigopreissin A (PAA), a fully protected form of the natural anigopreissin A, was found in our previous study to be active against several cancer cells, up to IC50 0.24 μM for HepG2 cells. Herein, a total of thirteen PAA analogues with variations in the number, position of substituents and unsaturation were synthesised starting from a common precursor, and their ability to induce cell growth inhibition was tested. By comparing the antiproliferative effect of the analogues with PAA and with the help of computational studies, we have gained valuable insights into both the biological activity and structure of this natural class of compounds. Indeed, we discovered the importance of the C-3 ring in modulating the biological activity of PAA, as well as the crucial role of the trans configuration of the styryl double bond and the significance of substitutions on the other parts of the molecule.