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

• Novel Dasatinib derivatives have been designed and synthesized.
• The cytotoxic activities of the compounds against cancer cell lines were evaluated.
• The compounds were screened for EGFR, SRC and ABL kinase inhibitory activity.
• The compounds may be promising leads to be developed as an alternative for CML.

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.

Three series of novel 4-benzothiazole amino quinazolines Dasatinib derivatives have been designed, synthesized and investigated for their cytotoxicity and kinase inhibitory activities.Figure optionsDownload as PowerPoint slide