Click Reaction as a Tool to Combine Pharmacophores: The Case of Vismodegib

被引：22

作者：

Christodoulou, Michael S. ^{[1
]}

Mori, Mattia ^{[2
]}

Pantano, Rebecca ^{[1
]}

Alfonsi, Romina ^{[3
]}

Infante, Paola ^{[2
]}

Botta, Maurizio ^{[4
,5
]}

Damia, Giovanna ^{[6
]}

Ricci, Francesca ^{[6
]}

Sotiropoulou, Panagiota A. ^{[7
]}

Liekens, Sandra ^{[8
]}

Botta, Bruno ^{[9
]}

Passarella, Daniele ^{[1
]}

机构：

[1] Univ Milan, Dipartimento Chim, I-20133 Milan, Italy

[2] Ist Italiano Tecnol, Ctr Life Nano Sci Sapienza, I-00161 Rome, Italy

[3] Univ Roma La Sapienza, Dept Mol Med, I-00161 Rome, Italy

[4] Univ Siena, Dipartimento Biotecnol Chim & Farm, I-53100 Siena, Italy

[5] Temple Univ, Sbarro Inst Canc Res & Mol Med, Coll Sci & Technol, Ctr Biotechnol, Philadelphia, PA 19122 USA

[6] IRCCS Ist Ric Farmacol Mario Negri, Dept Oncol, I-20156 Milan, Italy

[7] Univ Libre Bruxelles, IRIBHM, B-1070 Brussels, Belgium

[8] Katholieke Univ Leuven, Rega Inst Med Res, B-3000 Leuven, Belgium

[9] Univ Roma La Sapienza, Dipartimento Chim & Tecnol Farm, I-00185 Rome, Italy

来源：

CHEMPLUSCHEM | 2015年 / 80卷 / 06期

关键词：

cancer stem cells; click chemistry; docking; hedgehog pathway; vismodegib; HEDGEHOG SIGNALING PATHWAY; BASAL-CELL CARCINOMA; CONFORMER GENERATION; CANCER-CELLS; INHIBITOR; VALIDATION; RESISTANCE;

D O I：

10.1002/cplu.201402435

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

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.

引用

页码：938 / 943

页数：6

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