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Identification of new pyrrolo[2,3-d]pyrimidines as Src tyrosine kinase inhibitors in vitro active against Glioblastoma.
- Source :
-
European journal of medicinal chemistry [Eur J Med Chem] 2017 Feb 15; Vol. 127, pp. 369-378. Date of Electronic Publication: 2016 Dec 19. - Publication Year :
- 2017
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Abstract
- In the last few years, several pyrrolo-pyrimidine derivatives have been either approved by the US FDA and in other countries for the treatment of different diseases or are currently in phase I/II clinical trials. Herein we present the synthesis and the characterization of a novel series of pyrrolo[2,3-d]pyrimidines, compounds 8a-j, and their activity against Glioblastoma multiforme (GBM). Docking studies and MM-GBSA analysis revealed the ability of such compounds to efficiently interact with the ATP binding site of Src. Enzymatic assays against a mini-panel of kinases (Src, Fyn, EGFR, Kit, Flt3, Abl, AblT315I) have been performed, showing an unexpected selectivity of our pyrrolo[2,3-d]pyrimidines for Src. Finally, the derivatives were tested for their antiproliferative potency on U87 GBM cell line. Compound 8h showed a considerable cytotoxicity effect against U87 cell line with an IC <subscript>50</subscript> value of 7.1 μM.<br /> (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)
- Subjects :
- Antineoplastic Agents chemical synthesis
Antineoplastic Agents chemistry
Antineoplastic Agents metabolism
Antineoplastic Agents pharmacology
Cell Line, Tumor
Humans
Molecular Docking Simulation
Protein Conformation
Protein Kinase Inhibitors chemical synthesis
Protein Kinase Inhibitors chemistry
Protein Kinase Inhibitors metabolism
Protein Kinase Inhibitors pharmacology
Pyrimidines chemical synthesis
Pyrimidines metabolism
Structure-Activity Relationship
src-Family Kinases chemistry
src-Family Kinases metabolism
Drug Design
Glioblastoma pathology
Pyrimidines chemistry
Pyrimidines pharmacology
src-Family Kinases antagonists & inhibitors
Subjects
Details
- Language :
- English
- ISSN :
- 1768-3254
- Volume :
- 127
- Database :
- MEDLINE
- Journal :
- European journal of medicinal chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 28076826
- Full Text :
- https://doi.org/10.1016/j.ejmech.2016.12.036