New Quinoxaline Derivatives as Dual Pim-1/2 Kinase Inhibitors: Design, Synthesis and Biological Evaluation
Proviral integration site for Moloney murine leukemia virus (Pim)-1/2 kinase overexpression has been identified in a variety of hematologic (e.g., multiple myeloma or acute myeloid leukemia (AML)) and solid (e.g., colorectal carcinoma) tumors, playing a key role in cancer progression, metastasis, an...
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MDPI AG
2021-02-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/26/4/867 |
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doaj-a0e34a16b11a4b37ba7ae3360def4efc2021-02-07T00:03:01ZengMDPI AGMolecules1420-30492021-02-012686786710.3390/molecules26040867New Quinoxaline Derivatives as Dual Pim-1/2 Kinase Inhibitors: Design, Synthesis and Biological EvaluationBruno Oyallon0Marie Brachet-Botineau1Cédric Logé2Thomas Robert3Stéphane Bach4Sajida Ibrahim5William Raoul6Cécile Croix7Pascal Berthelot8Jean Guillon9Noël Pinaud10Fabrice Gouilleux11Marie-Claude Viaud-Massuard12Caroline Denevault-Sabourin13EA GICC-ERL 7001 CNRS, Team IMT, University of Tours, F-37200 Tours, FranceCNRS ERL7001 LNOx-EA GICC, University of Tours, F-37000 Tours, FranceDepartment of Medicinal Chemistry, IICIMED-EA1155, IRS2, University of Nantes, F-44200 Nantes, FranceIntegrative Biology of Marine Models Laboratory (LBI2M), Sorbonne University, CNRS, UMR8227, F-29680 Roscoff, FranceIntegrative Biology of Marine Models Laboratory (LBI2M), Sorbonne University, CNRS, UMR8227, F-29680 Roscoff, FranceEA GICC-ERL 7001 CNRS, Team PATCH, University of Tours, F-37200 Tours, FranceEA GICC-ERL 7001 CNRS, Team PATCH, University of Tours, F-37200 Tours, FranceEA GICC-ERL 7001 CNRS, Team IMT, University of Tours, F-37200 Tours, FranceUMR-S 1172-JPArc, University of Lille, INSERM, CHU Lille, F-59000 Lille, FranceARNA Laboratory, University of Bordeaux, INSERM U12132-UMR CNRS 5320, F-33076 Bordeaux, FranceISM, University of Bordeaux, CNRS, UMR 5255, F-33405 Talence, FranceCNRS ERL7001 LNOx-EA GICC, University of Tours, F-37000 Tours, FranceEA GICC-ERL 7001 CNRS, Team IMT, University of Tours, F-37200 Tours, FranceEA GICC-ERL 7001 CNRS, Team IMT, University of Tours, F-37200 Tours, FranceProviral integration site for Moloney murine leukemia virus (Pim)-1/2 kinase overexpression has been identified in a variety of hematologic (e.g., multiple myeloma or acute myeloid leukemia (AML)) and solid (e.g., colorectal carcinoma) tumors, playing a key role in cancer progression, metastasis, and drug resistance, and is linked to poor prognosis. These kinases are thus considered interesting targets in oncology. We report herein the design, synthesis, structure–activity relationships (SAR) and in vitro evaluations of new quinoxaline derivatives, acting as dual Pim1/2 inhibitors. Two lead compounds (<b>5c</b> and <b>5e</b>) were then identified, as potent submicromolar Pim-1 and Pim-2 inhibitors. These molecules were also able to inhibit the growth of the two human cell lines, MV4-11 (AML) and HCT-116 (colorectal carcinoma), expressing high endogenous levels of Pim-1/2 kinases.https://www.mdpi.com/1420-3049/26/4/867quinoxalinePim kinaseskinase inhibitoranticancer targeted therapy |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Bruno Oyallon Marie Brachet-Botineau Cédric Logé Thomas Robert Stéphane Bach Sajida Ibrahim William Raoul Cécile Croix Pascal Berthelot Jean Guillon Noël Pinaud Fabrice Gouilleux Marie-Claude Viaud-Massuard Caroline Denevault-Sabourin |
| spellingShingle |
Bruno Oyallon Marie Brachet-Botineau Cédric Logé Thomas Robert Stéphane Bach Sajida Ibrahim William Raoul Cécile Croix Pascal Berthelot Jean Guillon Noël Pinaud Fabrice Gouilleux Marie-Claude Viaud-Massuard Caroline Denevault-Sabourin New Quinoxaline Derivatives as Dual Pim-1/2 Kinase Inhibitors: Design, Synthesis and Biological Evaluation Molecules quinoxaline Pim kinases kinase inhibitor anticancer targeted therapy |
| author_facet |
Bruno Oyallon Marie Brachet-Botineau Cédric Logé Thomas Robert Stéphane Bach Sajida Ibrahim William Raoul Cécile Croix Pascal Berthelot Jean Guillon Noël Pinaud Fabrice Gouilleux Marie-Claude Viaud-Massuard Caroline Denevault-Sabourin |
| author_sort |
Bruno Oyallon |
| title |
New Quinoxaline Derivatives as Dual Pim-1/2 Kinase Inhibitors: Design, Synthesis and Biological Evaluation |
| title_short |
New Quinoxaline Derivatives as Dual Pim-1/2 Kinase Inhibitors: Design, Synthesis and Biological Evaluation |
| title_full |
New Quinoxaline Derivatives as Dual Pim-1/2 Kinase Inhibitors: Design, Synthesis and Biological Evaluation |
| title_fullStr |
New Quinoxaline Derivatives as Dual Pim-1/2 Kinase Inhibitors: Design, Synthesis and Biological Evaluation |
| title_full_unstemmed |
New Quinoxaline Derivatives as Dual Pim-1/2 Kinase Inhibitors: Design, Synthesis and Biological Evaluation |
| title_sort |
new quinoxaline derivatives as dual pim-1/2 kinase inhibitors: design, synthesis and biological evaluation |
| publisher |
MDPI AG |
| series |
Molecules |
| issn |
1420-3049 |
| publishDate |
2021-02-01 |
| description |
Proviral integration site for Moloney murine leukemia virus (Pim)-1/2 kinase overexpression has been identified in a variety of hematologic (e.g., multiple myeloma or acute myeloid leukemia (AML)) and solid (e.g., colorectal carcinoma) tumors, playing a key role in cancer progression, metastasis, and drug resistance, and is linked to poor prognosis. These kinases are thus considered interesting targets in oncology. We report herein the design, synthesis, structure–activity relationships (SAR) and in vitro evaluations of new quinoxaline derivatives, acting as dual Pim1/2 inhibitors. Two lead compounds (<b>5c</b> and <b>5e</b>) were then identified, as potent submicromolar Pim-1 and Pim-2 inhibitors. These molecules were also able to inhibit the growth of the two human cell lines, MV4-11 (AML) and HCT-116 (colorectal carcinoma), expressing high endogenous levels of Pim-1/2 kinases. |
| topic |
quinoxaline Pim kinases kinase inhibitor anticancer targeted therapy |
| url |
https://www.mdpi.com/1420-3049/26/4/867 |
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