Targeting Cancer Cells With Triazene-Appended Morpholine Chalcones: Antiproliferative Activity and ROS-Dependent Apoptotic Mechanisms

Abstract

Cancer is an extremely diverse and unpredictable disease on multiple levels. To find novel compounds with anticancer therapeutic potential, we designed and synthesised a library of triazene-appended morpholine chalcones and screened their activity against breast, lung and colorectal cancer cell lines. (E)-1-{4-[(E)-morpholinodiazenyl]phenyl}-3-(3,4,5-trimethoxyphenyl)prop-2-en-1-one (Compound 22) displayed notable cytotoxicity against human breast cancer cells (MDA-MB-231) and colon cancer cells (SW480), with IC50 values of 20 and 12.5 µM, respectively. Interestingly, when tested on non-cancerous HEK-293T cell lines, Compound 22 exhibited minimal or no cytotoxic effects, indicating its safety towards non-transformed cells. Furthermore, Rhodamine 123 and 2′,7′-dichlorodihydrofluorescein diacetate (DCFH-DA) staining assays revealed that Compound 22 induces apoptosis through the intrinsic pathway involving mitochondria and reactive oxygen species (ROS) generation, as supported by other staining assays. The compound also arrests the cell cycle at the G1 phase and inhibits cell migration and invasion. Taken together, this study reports that Compound 22 exhibits antiproliferative, apoptotic and anti-metastatic effects against breast and colon cancer.