Evaluation of anticancer activity of novel pyrimidine aniline molecular hybrids: Synthesis and characterization

Current study aims to develop a novel series of the substituted pyrimidine derivatives having anticancer potential. A novel series of pyrimidine derivatives were synthesized through a feasible method. 4-(2-chloroethyl)-2,5,6-trimethylpyrimidine (3) was prepared by condensation of (E)-N-(but-2-en-2-yl) acetamide (1) and 3-chloropropanenitrile (2) in presence of trifluoromethanesulfonic anhydride and 2-chloropyridine under reflux. Amination of previously generated pyrimidine alkyl chloride (3) with aromatic amines in the presence of triethyl amine and DMF resulted in formation of final product (4a-4j). All the synthesized derivatives were characterized by 1H NMR, 13C NMR and MASS spectral methods and the MTT assay evaluated their anticancer activity for five cancer cell lines. All the synthesized compounds were screened for anticancer activity against five cancer cell lines such as human cervical cancer (HeLa), breast cancer (MCF7), ovarian cancer (PA-1), colorectal carcinoma (LoVo) and human dermal fibroblasts (NHDF) cell lines. All the compounds displayed decent cytotoxicity profile when compared with the standard drug doxorubicin. Among the synthesized compounds (4a to 4j) tested, four compounds, 4e, 4d, 4g and 4j have demonstrated excellent cytotoxicity against cancer cell lines.