Synthesis, Biological Evaluation and Docking Study of New Pyrimidine Compounds as Anticancer Agents

Objectives The microtubule is composed of alpha beta tubulin heterodimers and is an attractive target for the design of anticancer drugs. Over the years, various compounds have been developed and their effect on tubulin polymerization has been studied. Despite a great efforts to make an effective drug, no drug has been introduced which inhibit Colchicine binding site. Methods In the current work a series of pyrimidine derivatives were designed and synthesized. Furthermore their cytotoxic activities were evaluated and molecular docking studies were performed. Twelve compounds of pyrimidine were synthesized in 3 different groups. In the first group, 4,6-diaryl pyrimidine was connected to the third aryl group via thio-methylene spacer. In the second group, this linker was substituted by sulfoxide-methylene moiety and in the third group sulfone-methylene group was used as spacer. Results The cytotoxic activity of these compounds were evaluated against 3 different cancerous cell lines (HT-29, MCF-7, T47D) as well as normal cell line (NIH3T3). Compounds in group 2 showed the best cytotoxicity and compound 7d showed the most potent cytotoxic activity against all cell lines. Molecular modelling studies revealed that compound 7d could strongly bind to the colchicine binding site of tubulin. Conclusion Altogether, with respect to obtained results, it is attractive and beneficial to further investigation on pyrimidine scaffold as antimitotic agents.