Design and synthesis of novel 4-benzothiazole amino quinazolines Dasatinib derivatives as potential anti-tumor agents.

Abstract

Three series of novel 4-benzothiazole amino quinazolines Dasatinib derivatives have been designed and synthesized. The entire target compounds were investigated for their in vitro cytotoxic activity by the MTT-based assay against 6 human cancer cell lines. Compared with the parental Dasatinib, most of the new compounds, especially 2, 4, 6-trimethylaniline series (3), demonstrated significant inhibitory activities against six cell lines. Furthermore, the target compounds were screened for Src and Abl kinase inhibitory activity. Among them, 1a, 1f and 3a-3f are more potential dual Src/Abl kinase inhibitors. Thus they may be promising lead compounds to be developed as an alternative for current Dasatinib therapy or for Imatinib-resistant patients, potentially via simultaneously blocking multiple RTK signaling pathways.

• Authors: Jin Cai, Min Sun, Xiaoqing Wu, Junqing Chen, Peng Wang, Xi Zong, Min Ji
• Journal: European journal of medicinal chemistry (Eur J Med Chem) Vol. 63 Pg. 702-12 (May 2013) ISSN: 1768-3254 [Electronic] France
• PMID: 23567960 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Chemical References

• Antineoplastic Agents
• Benzothiazoles
• Protein Kinase Inhibitors
• Pyrimidines
• Quinazolines
• Thiazoles
• Proto-Oncogene Proteins c-abl
• src-Family Kinases
• benzothiazole
• Dasatinib

Topics

• Antineoplastic Agents (chemical synthesis, chemistry, pharmacology)
• Benzothiazoles (chemistry)
• Cell Line, Tumor
• Cell Proliferation
• Cell Survival
• Dasatinib
• Dose-Response Relationship, Drug
• Drug Design
• HCT116 Cells
• Humans
• Inhibitory Concentration 50
• K562 Cells
• Models, Chemical
• Molecular Structure
• Protein Kinase Inhibitors (chemical synthesis, chemistry, pharmacology)
• Proto-Oncogene Proteins c-abl (antagonists & inhibitors, metabolism)
• Pyrimidines (chemistry)
• Quinazolines (chemical synthesis, chemistry, pharmacology)
• Thiazoles (chemistry)
• U937 Cells
• src-Family Kinases (antagonists & inhibitors, metabolism)