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

Area of Science:

• Medicinal Chemistry
• Pharmacology
• Cancer Biology

Background:

• Developing novel anticancer agents is crucial for effective cancer treatment.
• Dihydrotriazine derivatives represent a class of compounds with potential therapeutic applications.
• Targeting cancer cell proliferation, apoptosis, and autophagy are key strategies in cancer therapy.

Purpose of the Study:

• To design and synthesize novel dihydrotriazine derivatives.
• To evaluate the in vitro anticancer activity of these compounds against human cancer cell lines.
• To investigate the mechanism of action of the most potent compound, focusing on apoptosis and autophagy induction.

Main Methods:

• Synthesis of dihydrotriazine derivatives bearing 5-aryloxypyrazole moieties.
• In vitro antiproliferative activity assessment using the MTT assay against SGC-7901, HepG-2, and MCF-7 cancer cell lines.
• Analysis of reactive oxygen species (ROS) levels, apoptosis markers (Cl-PARP, Cl-caspase-3, Cl-caspase-9), and autophagy markers (LC3-II, Beclin-1) via relevant assays.

Main Results:

• Most synthesized compounds demonstrated significant antiproliferative effects on tested cancer cell lines.
• Compound 10e exhibited the most potent activity against HepG-2 cells, with an IC50 of 2.12 µM.
• Compound 10e induced significant apoptosis and autophagy in HepG-2 cells, evidenced by increased ROS, cleaved caspases, LC3-II, and Beclin-1 expression.

Conclusions:

• The designed dihydrotriazine derivatives, particularly compound 10e, possess potent anticancer properties.
• Compound 10e exerts its anticancer effects through the induction of apoptosis and autophagy in cancer cells.
• These findings suggest that dihydrotriazine derivatives are promising candidates for the development of novel anticancer therapeutics.