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

• Published in: Bioorganic & medicinal chemistry letters 2020-06, Vol.30 (11), p.127149-127149, Article 127149
• Main Authors: Homerin, Germain, Nica, Adrian Sorin, Farce, Amaury, Dubois, Joëlle, Ghinet, Alina
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - metabolism; Antineoplastic Agents - pharmacology; Binding Sites; Catalytic Domain; Cell Line, Tumor; Cell Survival - drug effects; Chalcone; Chalcones - chemistry; Chalcones - metabolism; Chalcones - pharmacology; Chemical Sciences; Claisen-Schmidt; Drug Screening Assays, Antitumor; Enzyme Inhibitors - chemical synthesis; Enzyme Inhibitors - metabolism; Enzyme Inhibitors - pharmacology; Farnesyltransferase; Farnesyltranstransferase - antagonists & inhibitors; Farnesyltranstransferase - metabolism; Humans; Inhibitor; Molecular Docking Simulation; Sonication; Structure-Activity Relationship; Ultrasounds
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2020.127149

[Display omitted] 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 (β-hydroxy-ketone, 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.