Structure-based drug design and biological evaluation of 2-acetamidobenzothiazole derivative as EGFR kinase inhibitor

Abstract

EGFR tyrosine kinase has been reported mainly in 40–80% of non-small lung cancers, in addition to colon and breast cancers. In this study, we illustrate the synthesis of a highly potent antitumor agent. The synthesized compound 4 was screened at NCI, USA, for antitumor activity against non-small lung cancer, colon cancer and breast cancer cell lines. Results indicated that this compound is more potent antitumor agent compared to erlotinib against all tested cell lines except breast cancer (MDA-MB-468) cell line. In addition, it was tested initially at a single dose concentration of 100 µM over 11 different kinases. At this concentration, 94.45% inhibition of the enzymatic activity of EGFR kinase was observed, while the inhibition in activity was below 55% in all other kinases. Compound 4 was further tested in a 10-dose IC₅₀ mode and showed IC₅₀ value of 0.239 µM for EGFR kinase. In vivo acute toxicity of this compound was also tested.

• Acetamidobenzothiazole
• breast cancer
• colon cancer
• non-small lung cancer
• EGFR tyrosine kinase inhibitor
• in vivo acute toxicity

Acknowledgements

The authors would like to express their sincere thanks to the staff members of the Department of Health and Human Services, National Cancer Institute (NCI), Bethesda, Maryland, USA for performing the antitumor testing of the newly synthesized compound. Thanks to Reaction Biology Corporation, USA for performing the kinase profile assay.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

Supplementary material available online

Supplementary Figures S1–S4 and Table S1