Design and Synthesis of Tubulin and Histone Deacetylase Inhibitor Based on iso-Combretastatin A-4.
Diana LamaaHsin-Ping LinLena ZigCyril BauvaisGuillaume BollotJérôme BignonHelene LevaiqueOlivier PamlardJoelle DuboisMehdi OuaissiMartin SouceAthena KasselouriFrançois SallerDelphine BorgelChantal Jayat-VignolesHazar Al-MouhammadJean FeuillardKarim BenihoudMouad AlamiAbdallah HamzePublished in: Journal of medicinal chemistry (2018)
Designing multitarget drugs have raised considerable interest due to their advantages in the treatment of complex diseases such as cancer. Their design constitutes a challenge in antitumor drug discovery. The present study reports a dual inhibition of tubulin polymerization and HDAC activity. On the basis of 1,1-diarylethylenes ( isoCA-4) and belinostat, a series of hybrid molecules was successfully designed and synthesized. In particular compounds, 5f and 5h were proven to be potent inhibitors of both tubulin polymerization and HDAC8 leading to excellent antiproliferative activity.