Structure–activity relationship studies on a novel class of antiproliferative agents derived from Lavendustin A. Part I: Ring A modifications

The potent antiproliferative agent SDZ LAP 977, which has shown efficacy in a clinical proof of concept study in actinic keratosis patients, has been previously demonstrated to block the cell cycle in mitosis. In the present study, we further explored the mode of action: SDZ LAP 977 binds to the “colchicine binding site” on tubulin and, thus, inhibits tubulin polymerization in vitro. Moreover, we established structure–activity relationships for the effect of modifications in the 2,5-dimethoxyphenyl moiety (“ring A”) of the molecule on in vitro antiproliferative activity.

The SAR of A-ring modified analogues of a novel class of antiproliferative agents and studies on the mode of action of compound 1 are described and discussed.Figure optionsDownload as PowerPoint slide