Novel Triazole–Diquinothiazine Hybrids Modulating Apoptosis and Stress Pathways in Colorectal Cancer Cells

Abstract

Background/Objectives: Colorectal cancer is one of the most common malignancies worldwide and is frequently associated with dysregulation of apoptosis, oxidative stress, and the p53 regulatory axis. The development of novel compounds capable of modulating these pathways remains an important challenge in anticancer drug discovery. This study aimed to evaluate the biological activity of newly synthesized triazole–diquinothiazine derivatives in colorectal cancer cells and to identify the most promising lead compound for further development. Methods: The synthesized derivatives were evaluated in HCT116 colorectal cancer cells harboring wild-type TP53 and in normal BEAS-2B cells. Cytotoxicity, apoptosis, cell cycle distribution, intracellular reactive oxygen species (ROS) generation, and the expression of genes associated with apoptosis, oxidative stress, and inflammatory response were analyzed. Results: The investigated compounds exhibited diverse biological effects, including modulation of apoptosis, cell cycle progression, and oxidative stress. Among the tested derivatives, compound B5 demonstrated the most favorable biological profile, characterized by a more pronounced biological response in HCT116 cells than in BEAS-2B cells, increased ROS generation, reduced MDM2 expression, and a marked induction of early apoptosis. Conclusions: The obtained results indicate that triazole–diquinothiazine derivatives represent promising lead structures for further optimization. In particular, compound B5 warrants additional mechanistic and preclinical studies to evaluate its potential as a candidate for colorectal cancer therapy.