Design, synthesis, and biological evaluation of novel bromo-pyrimidine analogues as tyrosine kinase inhibitors

Abstract

In the present investigation we designed, synthesized and evaluated a novel series of bromo-pyrimidine analogues (6a-j, 7a-e, 9a-f, and 10a-f) as anticancer agents. The compounds were characterized using spectroscopic studies and elemental analysis and screened for their in vitro cytotoxic activity by MTT assay against four cancer cell lines including HCT116 (human colon cancer cell line), A549 (human lung cancer cell line), K562 (human chronic myeloid leukemia cell line), U937 (human acute monocytic myeloid leukemia cell line) as well as the normal human liver cell line, L02. Most of the compounds showed potent activity on K562 cells. Considering this, the compounds were evaluated for Bcr/Abl tyrosine kinase inhibitory activity by ADP-Glo assay. Dasatinib was used as standard drug for both cytotoxicity and tyrosine kinase inhibition studies. The compounds, 6g, 7d, 9c, and 10e emerged as potent Bcr/Abl kinase inhibitors. Hence, the potent compounds that arose out of this investigation are potential lead molecules to develop as an alternative to existing dasatinib therapy.

Keywords

• Anticancer
• Bromo-pyrimidine
• Cytotoxicity
• Dasatinib derivatives
• MTT assay
• Bcr/Abl tyrosine kinase