Dihydrotriazine derivatives display high anticancer activity and inducing apoptosis, ROS, and autophagy.

Series of dihydrotriazine derivatives bearing 5-aryloxypyrazole moieties were identified as novel anticancer agents. [Display omitted] • Compound 10e displayed better activity than commercial drugs (5-Fu), with an IC 50 value of 2.12 µM for HepG-2 cells. • Compound 10e could enhance the expression of Cl-PARP, Cl-caspase-3 and Cl-caspase-9. • 10e triggered the formation of autophagosomes by promoting the expression of LC3-II and Beclin-1. A series of dihydrotriazine derivatives bearing 5-aryloxypyrazole moieties were designed, and their anticancer activities against three human cancer cell lines (SGC-7901, HepG-2 and MCF-7) and one non-cancer cell line (LO2) were explored using the MTT assay in vitro. Most of the compounds exhibited potent antiproliferative activities against the three cancer cell lines, with compound 10e (IC 50 = 2.12 µM) exhibiting the most potent antiproliferative activity against HepG-2 cells. Interestingly, autophagy was observed in the 10e -treated HepG-2 cells. Compound 10e also increased reactive oxygen species (ROS) levels and resulted in marked HepG-2 cells apoptosis. Further studies revealed that compound 10e could enhance the expression of Cl-PARP, Cl-caspase-3, and Cl-caspase-9. In addition, 10e triggered the formation of autophagosomes by promoting LC3-II and Beclin-1 expression. These results might be useful for exploring and developing dihydrotriazine derivatives as novel anticancer agents. [ABSTRACT FROM AUTHOR]