Targeting Cancer Cells With Triazene-Appended Morpholine Chalcones: Antiproliferative Activity and ROS-Dependent
Ahammed Ameen Thottasseri1, Sathyapriya Chandramohan2, Rajesh Ravichandran2
1Department of Chemistry, Pondicherry University, Puducherry, India.
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.
Insights
A novel compound, Compound 22, shows significant anticancer effects against breast and colon cancer cells. It induces apoptosis and inhibits cancer cell migration and invasion, with minimal toxicity to normal cells.
Area of Science:
- Medicinal Chemistry
- Cancer Biology
- Pharmacology
Background:
- Cancer is a complex disease requiring novel therapeutic strategies.
- Triazene-appended morpholine chalcones are explored for anticancer potential.
Purpose of the Study:
- To design, synthesize, and evaluate novel triazene-appended morpholine chalcones as anticancer agents.
- To identify specific compounds with potent and selective activity against cancer cell lines.
Main Methods:
- Synthesis of a library of triazene-appended morpholine chalcones.
- Screening of compounds against breast, lung, and colorectal cancer cell lines.
- Cytotoxicity assays (IC50 determination) and apoptosis induction studies (Rhodamine 123, DCFH-DA staining).
- Cell cycle analysis and cell migration/invasion assays.
Main Results:
- Compound 22 demonstrated significant cytotoxicity against MDA-MB-231 (breast) and SW480 (colon) cancer cells (IC50 values 20 µM and 12.5 µM, respectively).
- Compound 22 showed minimal toxicity to non-cancerous HEK-293T cells.
- Apoptosis induction via the intrinsic mitochondrial pathway and reactive oxygen species (ROS) generation was confirmed.
- Cell cycle arrest at the G1 phase and inhibition of cell migration and invasion were observed.
Conclusions:
- Compound 22 exhibits potent antiproliferative, apoptotic, and anti-metastatic effects against breast and colon cancer.
- The compound's selectivity for cancer cells suggests therapeutic potential.
- Further investigation into Compound 22 as an anticancer therapeutic is warranted.
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