Synthesis and anticancer activity evaluation of novel azacalix[2]arene[2]pyrimidines

A series of novel azacalix[2]arene[2]pyrimidines were synthesized, and evaluated for their antiproliferative activities against A549, MCF7, SH-SY5Y and CNE human cancer cell lines in vitro by using the CCK-8 assay. A number of compounds showed low micromolar antiproliferative activities against MCF7 cell line. Compound 4j, containing a pyrrolidine moiety, exhibited the strongest inhibitory activity with an IC50 value of 0.58 μM. Furthermore, breast cancer cells were used to explore the inhibition mechanism of these azacalix[2]arene[2]pyrimidines. The results suggested these compounds were involved in inducing cell apoptosis via up-regulation of caspase-3 and caspase-9 protein expression, and the cell cycle was arrested at the S phase. Our reports here represent the first studies on the biological activities of azacalix[2]arene[2]pyrimidines. Novel azacalix[2]arene[2]pyrimidines were designed and synthesized. Compound 4j exhibited strong inhibitory activity against MCF7 cells, and its mechanisms were involved in inducing apoptosis via up-regulation of caspase-3 and caspase-9 cell and cycle arrest at the S phase. [Display omitted] •21 Novel azacalix[2]arene[2]pyrimidines were synthesized.•Their antiproliferative activities were evaluated.•Compounds 4j, 4n and 4r exhibited significant anticancer activities.•Compound 4j induced cell cycle arrest and apoptosis in MCF-7 cells.