2. Academic Validation
  3. Synthesis and biological evaluation of thiophene and benzo[b]thiophene analogs of combretastatin A-4 and isocombretastatin A-4: A comparison between the linkage positions of the 3,4,5-trimethoxystyrene unit

Synthesis and biological evaluation of thiophene and benzo[b]thiophene analogs of combretastatin A-4 and isocombretastatin A-4: A comparison between the linkage positions of the 3,4,5-trimethoxystyrene unit

  • Bioorg Med Chem Lett. 2016 Jan 1;26(1):174-80. doi: 10.1016/j.bmcl.2015.11.010.
Cong Viet Do 1,  Abdelfattah Faouzi 1,  Caroline Barette 2,  Amaury Farce 3,  Marie-Odile Fauvarque 2,  Evelyne Colomb 4,  Laura Catry 1,  Odile Berthier-Vergnes 5,  Marek Haftek 4,  Roland Barret 1,  Thierry Lomberget 6
Affiliations

Affiliations

  • 1 Université de Lyon, Université Lyon 1, Faculté de Pharmacie - ISPB, EA 4446 Biomolécules, Cancer et Chimiorésistances, SFR Santé Lyon-Est CNRS UMS3453 - INSERM US7, 8 avenue Rockefeller, F-69373 Lyon Cedex 08, France.
  • 2 Univ. Grenoble Alpes, iRTSV-BGE, F-38000 Grenoble, France; CEA, iRTSV-BGE, F-38000 Grenoble, France; INSERM U1038, BGE, F-38000 Grenoble, France.
  • 3 Univ Lille Nord de France, F-59000 Lille, France; Institut de Chimie Pharmaceutique Albert Lespagnol, EA GRIIOT (4481), IFR114, 3 Rue du Pr Laguesse, B.P. 83, F-59006 Lille, France.
  • 4 Université Lyon 1, Faculté de Médecine et de Pharmacie, EA 4169 «Fundamental, Clinical and Therapeutic Aspects of the Skin Barrier Function», 8 avenue Rockefeller, F-69373 Lyon Cedex 08, France.
  • 5 Université de Lyon, Université Lyon 1, Centre de Génétique et de Physiologie Moléculaires et Cellulaires, CNRS UMR5534 - Université Lyon 1, 43 Bd du 11 Novembre 1918, 69622 Villeurbanne Cedex, France.
  • 6 Université de Lyon, Université Lyon 1, Faculté de Pharmacie - ISPB, EA 4446 Biomolécules, Cancer et Chimiorésistances, SFR Santé Lyon-Est CNRS UMS3453 - INSERM US7, 8 avenue Rockefeller, F-69373 Lyon Cedex 08, France. Electronic address: thierry.lomberget@univ-lyon1.fr.
PMID: 26602281 DOI: 10.1016/j.bmcl.2015.11.010
Abstract

Combretastatin A-4 and isocombretastatin A-4 derivatives having thiophenes or benzo[b]thiophenes instead of the B ring were prepared and evaluated for their in cellulo tubulin polymerization inhibition (TPI) and antiproliferative activities. The presence of the benzo[b]thiophene ring proved to have a crucial effect as most of the thiophene derivatives, except those having one methoxy group, were inactive to inhibit tubulin polymerization into microtubules. The influence of the attachment position was also studied: benzo[b]thiophenes having iso or cis 3,4,5-trimethoxystyrenes at position 2 were 12-30-fold more active than the 3-regioisomers for the TPI activity. Some of the novel designed compounds exhibited interesting anti-proliferative effects on two different cell lines.

Keywords

Antiproliferative agents; Combretastatin A-4; Heterocycles; Inhibitors of tubulin assembly; Melanocyte.

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