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

Abstract

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 μM, 21.02 μM, 24.67 μM, 22.13 μM 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 μM 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