Design, Synthesis, and In vitro Anticancer Activity of Novel Chrysin Derivatives

Background Cancer is a serious threaten to human life, and drug developers are pushing hard to discover potent anticancer agents. Pyrimidine and flavonoids are both attractive entities in medicinal chemistry; it is necessary to get new cancer drugs capitalizing on the two frameworks. Objective This work includes the synthesis of series chrysin derivatives containing different substituted pyrimidines and an evaluation of their in vitro anticancer activity. Methods Chrysin was merged with different substituted pyrimidines. Their antiproliferative activity was screened against five cancer cell lines (A549, HepG2, HCT116, MCF-7, and PC-3) using MTS method, and the marketed anticancer drug erlotinib was used as a reference. Results Seventeen chrysin derivatives were synthesized. Compound 33E showed the best activity against A549, HepG2, MCF-7, and PC-3 cells, with IC50 values of 30.30 & mu;M, 21.02 & mu;M, 24.67 & mu;M, 22.13 & mu;M in A549, HepG2, MCF-7, PC-3 cells, respectively. Compound 33A showed the best activity against HCT116 cells, with an IC50 value of 4.83 & mu;M in HCT116 cell lines. Conclusion In the present study, a new set of chrysin derivatives containing anilinopyrimidine, piperazine-pyrimidine and piperidine-pyrimidine were prepared. Two compounds (33D, 33E) display higher toxicity than erlotinib toward the five cancerous cell lines (A549, HepG2, HCT116, MCF-7, and PC-3), and one compound (33A) exhibits better inhibitory activity than erlotinib to the HCT116 cells. These results underline the significance of the strategy to merge chrysin with different substituted pyrimidines for obtaining efficient anticancer drugs.