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Click Reaction as a Tool to Combine Pharmacophores: The Case of Vismodegib
Author(s) -
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
Publication year - 2015
Publication title -
chempluschem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.801
H-Index - 61
ISSN - 2192-6506
DOI - 10.1002/cplu.201402435
Subject(s) - vismodegib , smoothened , hedgehog signaling pathway , pharmacophore , chemistry , hedgehog , click chemistry , triazole , cancer research , stereochemistry , combinatorial chemistry , computational biology , biochemistry , biology , signal transduction , organic chemistry
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.