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

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

  • J Med Chem. 2018 Aug 9;61(15):6574-6591. doi: 10.1021/acs.jmedchem.8b00050.
Diana Lamaa 1,  Hsin-Ping Lin 1,  Lena Zig 2,  Cyril Bauvais 3,  Guillaume Bollot 3,  Jérôme Bignon 4,  Helene Levaique 4,  Olivier Pamlard 4,  Joelle Dubois 4,  Mehdi Ouaissi 5,  Martin Souce 6,  Athena Kasselouri 6,  François Saller 7,  Delphine Borgel 7,  Chantal Jayat-Vignoles 8,  Hazar Al-Mouhammad 8,  Jean Feuillard 8 9,  Karim Benihoud 2,  Mouad Alami 1,  Abdallah Hamze 1
Affiliations

Affiliations

  • 1 BioCIS , Univ. Paris-Sud, CNRS, équipe labellisée Ligue Contre le Cancer, Université Paris-Saclay , 92290 Châtenay-Malabry , France.
  • 2 Vectorologie et thérapeutiques anticancéreuses, UMR 8203 CNRS , Univ. Paris-Sud, Institut Gustave Roussy , Université Paris-Saclay, Villejuif 94805 , France.
  • 3 SYNSIGHT , 86 rue de Paris , Orsay 91400 , France.
  • 4 CIBI platform , Institut de Chimie des Substances Naturelles , UPR 2301, CNRS avenue de la terrasse , F-91198 Gif sur Yvette , France.
  • 5 CHRU Hôpital de Tours Trousseau , Service de chirurgie digestive, oncologique, endocrinienne et de transplantation hépatique , avenue de la République , 37170 Chambray-lès-Tours , France.
  • 6 Lip(Sys)2, Chimie Analytique Pharmaceutique , Univ Paris-Sud, Université Paris-Saclay , F-92290 Châtenay-Malabry , France.
  • 7 INSERM, UMR-S1176 , University Paris-Saclay , F-94276 Le Kremlin-Bicêtre , France.
  • 8 Univ Limoges, Faculté de Médecine , CNRS UMR 7276, Laboratoire CRIBL , F-87025 Limoges , France.
  • 9 CHU Limoges, Hôpital Dupuytren , Service d'hématologie , F-87025 Limoges , France.
PMID: 30004697 DOI: 10.1021/acs.jmedchem.8b00050
Abstract

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.

Figures