Ultrasounds-mediated 10-seconds synthesis of chalcones as potential farnesyltransferase inhibitors

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:30

Article

Homerin, Germain¹  Nica, Adrian Sorin^1,2  Farce, Amaury³  Dubois, Joelle⁴  Ghinet, Alina^1,2,5 

[1] UCLille, Yncrea Hauts France, Lab Sustainable Chem & Hlth, Hlth & Environm Dept,Team Sustainable Chem,Ecole, 13 Rue Toul, F-59046 Lille, France

[2] Univ Lille, INSERM, U1167 RID AGE Facteurs Risque & Determinants Mol, CHU Lille,Inst Pasteur Lille, F-59000 Lille, France

[3] Fac Sci Pharmaceut & Biol Lille, F-59006 Lille, France

[4] CNRS, Inst Chim Subst Nat, UPR2301, Ctr Rech Gif, Ave Terrasse, F-91198 Gif Sur Yvette, France

[5] Alexandru Ioan Cuza Univ, Fac Chem, Bd Carol 1,11, Iasi 700506, Romania

关键词: Farnesyltransferase;    Inhibitor;    Chalcone;    Claisen-Schmidt;    Ultrasounds;   

DOI  :  10.1016/j.bmcl.2020.127149

来源: Elsevier

【 摘 要 】

A broad range of chalcones and derivatives were easily and rapidly synthesized, following Claisen-Schmidt condensation of (hetero)aryl ketones and (hetero)aryl aldehydes using a ultrasound probe. A comparison was made with classical magnetic stirring experiments, and an optimization study was realized, showing lithium hydroxide to be the best basic catalyst of the studied condensations. By-products of the reactions (beta-hydroxyketone, diketones, and cyclohexanols) were also isolated. All compounds were evaluated in vitro for their ability to inhibit human farnesyltransferase, a protein implicated in cancer and rare diseases and on the NCI-60 cancer cell lines panel. Molecules showed inhibitory activity on the target protein and cytostatic effect on different cell lines with particular activity against MCF7, breast cancer cells.

【 授权许可】

Free