The microtubule is composed of αβ-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 great efforts to make an effective drug, no drug has
been introduced which inhibit colchicine binding site. 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. Twenty compounds of pyrimidine were synthesized in 2 different
groups. In the first group, 4,6-diaryl pyrimidine was connected to the third aryl group via thiomethylene
spacer. In the second group, this linker was substituted by S-CH2-triazole moiety. The cytotoxic
activity of these compounds was evaluated against 4 different cell lines (HT-29, MCF-7, T47D,
NIH3T3). Compounds 6d, 6m, 6p showed potent cytotoxic activity against MCF7 cancerous cell lines.
Between these compounds, compound 6p did not show cytotoxic activity against NIH- 3T3 (normal
cell) cell line. Docking studies show that these compounds occupy colchicine binding site in tubulin
protein and probably their anticancer mechanism is inhibition of tubulin polymerization. Altogether,
with respect to obtained results, it is attractive and beneficial to further investigation on pyrimidine
scaffold as antimitotic agents. Attention to the selectivity index of 6p on MCF7 cell line could be valuable
in design new chemical agents for the treatment of breast cancer.