American Chemical Society
Browse

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

Download (2.22 kB)
dataset
posted on 2018-07-13, 00:00 authored by Diana Lamaa, Hsin-Ping Lin, Lena Zig, Cyril Bauvais, Guillaume Bollot, Jérôme Bignon, Helene Levaique, Olivier Pamlard, Joelle Dubois, Mehdi Ouaissi, Martin Souce, Athena Kasselouri, François Saller, Delphine Borgel, Chantal Jayat-Vignoles, Hazar Al-Mouhammad, Jean Feuillard, Karim Benihoud, Mouad Alami, Abdallah Hamze
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.

History