Design and Synthesis of Tubulin and Histone Deacetylase Inhibitor Based on <i>iso</i>-Combretastatin A‑4

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 (<i>iso</i>CA-4) and belinostat, a series of hybrid molecules was successfully designed and synthesized. In particular compounds, <b>5f</b> and <b>5h</b> were proven to be potent inhibitors of both tubulin polymerization and HDAC8 leading to excellent antiproliferative activity