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Published on: May 11, 2018
Urea-functionalized organoselenium compounds as promising anti-HepG2 and apoptosis-inducing agents
Fardous F El-Senduny1, Sameh M Shabana2, Daniel Rösel3,4
1Department of Chemistry, Biochemistry Division, Faculty of Science, Mansoura University, Mansoura, Egypt.
Abstract:
Hepatocellular carcinoma is a highly aggressive and difficult-to-treat type of cancer. Incorporating urea functionality into the backbone of organoselenium compounds is expected to develop promising chemotherapeutic leads against liver cancer. Methods: Urea-functionalized organoselenium compounds were synthesized in good yields, and their cytotoxicity was evaluated against HepG2 cells. Results: 1,1'-(Diselanediylbis(4,1-phenylene))bis(3-phenylurea) (14) exhibited efficient anti-HepG2 activity in sub-micromolar concentrations, with no toxicity to normal human skin fibroblasts. The molecular mechanisms of the diselenide-based urea 14 were evaluated using colony formation, wound healing, 3D spheroid invasion assays, cell cycle analysis and apoptosis induction. Its redox properties were also assessed by using different bioassays. Conclusion: Our study revealed promising anticancer, antimigratory and anti-invasiveness properties of 1,1'-(diselanediylbis(4,1-phenylene))bis(3-phenylurea) (14) against HepG2.
Insights
Researchers developed a novel urea-functionalized organoselenium compound that shows potent anticancer activity against hepatocellular carcinoma (liver cancer) cells. This compound effectively inhibits cancer cell growth and migration without harming normal cells.
Area of Science:
- Medicinal Chemistry
- Oncology
- Organoselenium Chemistry
Background:
- Hepatocellular carcinoma (HCC) is an aggressive cancer with limited treatment options.
- Organoselenium compounds offer potential as chemotherapeutic agents.
- Introducing urea functionality may enhance anticancer efficacy.
Purpose of the Study:
- To synthesize and evaluate urea-functionalized organoselenium compounds for anticancer activity against HCC.
- To investigate the molecular mechanisms underlying the efficacy of promising compounds.
- To assess the safety profile of the lead compound.
Main Methods:
- Synthesis of urea-functionalized organoselenium compounds.
- Cytotoxicity assays using HepG2 (liver cancer) cells and normal human skin fibroblasts.
- Evaluation of anticancer mechanisms including colony formation, wound healing, 3D spheroid invasion, cell cycle analysis, and apoptosis induction.
- Assessment of redox properties.
Main Results:
- Compound 14, 1,1'-(diselanediylbis(4,1-phenylene))bis(3-phenylurea), demonstrated potent anti-HepG2 activity at sub-micromolar concentrations.
- Compound 14 showed no toxicity towards normal human skin fibroblasts.
- Mechanism studies indicated anticancer, antimigratory, and anti-invasiveness properties.
Conclusions:
- 1,1'-(Diselanediylbis(4,1-phenylene))bis(3-phenylurea) is a promising lead compound for developing novel therapies against hepatocellular carcinoma.
- The compound exhibits significant anticancer effects with a favorable safety profile.
- Further research into its mechanisms and therapeutic potential is warranted.
