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

J Med Chem 2018 Aug 26;61(15):6574-6591. Epub 2018 Jul 26.

BioCIS , Univ. Paris-Sud, CNRS, équipe labellisée Ligue Contre le Cancer, Université Paris-Saclay , 92290 Châtenay-Malabry , France.

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.

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http://dx.doi.org/10.1021/acs.jmedchem.8b00050DOI Listing
August 2018
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