2. Academic Validation
  3. Combretastatin A-4 sulfur-containing heterocyclic derivatives: Synthesis, antiproliferative activities and molecular docking studies

Combretastatin A-4 sulfur-containing heterocyclic derivatives: Synthesis, antiproliferative activities and molecular docking studies

  • Eur J Med Chem. 2021 Apr 5:215:113275. doi: 10.1016/j.ejmech.2021.113275.
Abdelfattah Faouzi 1,  Alexandre Arnaud 2,  Alexandre Bancet 2,  Caroline Barette 3,  Jordane Preto 4,  Cong Viet Do 5,  Lars Petter Jordheim 4,  Zineb Bousfiha 4,  Thi Thanh Binh Nguyen 6,  Marion Verrière 2,  Amaury Farce 7,  Marie-Odile Fauvarque 3,  Roland Barret 2,  Thierry Lomberget 8
Affiliations

Affiliations

  • 1 Université de Lyon, Université Lyon 1, Faculté de Pharmacie, ISPB, EA 4446 Bioactive Molecules and Medicinal Chemistry, SFR Santé Lyon-Est CNRS UMS3453, INSERM US7, F-69373, Lyon Cedex 08, France; Present Address: Center for Clinical Pharmacology, St. Louis College of Pharmacy and Washington University School of Medicine, St. Louis, MO, USA.
  • 2 Université de Lyon, Université Lyon 1, Faculté de Pharmacie, ISPB, EA 4446 Bioactive Molecules and Medicinal Chemistry, SFR Santé Lyon-Est CNRS UMS3453, INSERM US7, F-69373, Lyon Cedex 08, France.
  • 3 Univ. Grenoble Alpes, CEA, Inserm, BGE U1038, 38000, Grenoble, France.
  • 4 Université de Lyon, Université Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Centre de Recherche en Cancérologie de Lyon, Lyon, 69008, France.
  • 5 Université de Lyon, Université Lyon 1, Faculté de Pharmacie, ISPB, EA 4446 Bioactive Molecules and Medicinal Chemistry, SFR Santé Lyon-Est CNRS UMS3453, INSERM US7, F-69373, Lyon Cedex 08, France; University of Science and Technology of HanoÏ USTH, 18 Hoang Quoc Viet, Hanoi, 100000, Viet Nam; Present Address: Faculty of Pharmacy, Dai Nam University, 56 Vu Trong Phung, Hanoi, Viet Nam.
  • 6 Université de Lyon, Université Lyon 1, Faculté de Pharmacie, ISPB, EA 4446 Bioactive Molecules and Medicinal Chemistry, SFR Santé Lyon-Est CNRS UMS3453, INSERM US7, F-69373, Lyon Cedex 08, France; Present Address: VNU School of Medicine and Pharmacy, 144 Xuan Thuy, Cau Giay, Hanoi, 100000, Viet Nam.
  • 7 Université de Lille, Inserm, CHU Lille, U995, LIRIC, Lille Inflammation Research International Center, F-59006 Lille Cedex, France.
  • 8 Université de Lyon, Université Lyon 1, Faculté de Pharmacie, ISPB, EA 4446 Bioactive Molecules and Medicinal Chemistry, SFR Santé Lyon-Est CNRS UMS3453, INSERM US7, F-69373, Lyon Cedex 08, France; Université de Lyon, Université Lyon 1, CNRS UMR 5246 Institut de Chimie et Biochimie Moléculaires et Supramoléculaires (ICBMS), Faculté de Pharmacie, ISPB, 8, Avenue Rockefeller, F-69373, Lyon, Cedex 08, France. Electronic address: thierry.lomberget@univ-lyon1.fr.
PMID: 33618157 DOI: 10.1016/j.ejmech.2021.113275
Abstract

Combretastatin A-4 inspired heterocyclic derivatives were synthesized and evaluated for their biological activities on tubulin polymerization and cell proliferation. Among the 19 described sulfur-containing compounds, derivatives (Z)-4h and (Z)-4j exhibited interesting in cellulo tubulin polymerization inhibition and antiproliferative activities with IC50 values for six different cell lines between 8 and 27 nM. Furthermore, in silico docking studies within the colchicine/CA-4 binding site of tubulin were carried out to understand the interactions of our products with the protein target. The effects on the cell cycle of follicular lymphoma cells were also investigated at 1-10 nM concentrations showing that apoptotic processes occurred.

Keywords

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

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