Click Reaction as a Tool to Combine Pharmacophores: The Case of Vismodegib. Issue 6 (27th February 2015)

• Record Type: Journal Article
• Authors: Christodoulou, Michael S.; Mori, Mattia; Pantano, Rebecca; Alfonsi, Romina; Infante, Paola; Botta, Maurizio; Damia, Giovanna; Ricci, Francesca; Sotiropoulou, Panagiota A.; Liekens, Sandra; Botta, Bruno; Passarella, Daniele
• Is Part Of: ChemPlusChem. Volume 80:Issue 6(2015:Jun.)
• Page Start: 938
• Page End: 943
• Publication Date: 2015-02-27
• Subjects: cancer stem cells -- click chemistry -- docking -- hedgehog pathway -- vismodegib; Chemistry -- Periodicals; 540.5
• DOI: 10.1002/cplu.201402435
• Languages: English
• ISSNs: 2192-6506

Abstract

Abstract: The design and the preparation of a small library of 1, 4‐diphenyl‐1, 2, 3‐triazole derivatives is reported, with the aim to obtain a new class of Hedgehog pathway inhibitors. The smoothened protein is part of the hedgehog signaling pathway that is inhibited by the lead compound Vismodegib. Based on molecular modeling simulations, seven triazole derivatives of Vismodegib are synthesized and their biological effect on different endothelial, cancer, and cancer stem cell lines is reported. Abstract : Mix and Click! Rational design, versatile synthesis, and biological evaluation of Vismodegib analogues has been achieved to confirm the 1, 2, 3‐triazole ring as a creative tool to combine pharmacophores. Interaction with the Hedgehog pathway and the ability to inhibit the formation of blood vessels are discussed (see figure).