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Synthesis of Phenol-derivatives and Biological Screening for Anticancer Activity
Anzhelika Karjalainen1, Phuong Doan1, Jerome G Chandraseelan1
1Molecular Signaling Lab, Computational Systems Biology Research Group, Department of Signal Processing, Tampere University of Technology, P.O.Box 553, 33101, Tampere. Finland.
Background:
Phenolic compounds are known for their cytotoxic properties against cancer cells despite their still unclear general mechanism of action. Herein is reported the evaluation of the cytotoxic effects of on human osteosarcoma cells of nine phenol derivatives against osteosarcoma cells, and some insights on their mechanism.
Method And Results:
The cytotoxicity was characterized by cell viability, scratch assay, cellular DNA content measurement, Annexin V apoptosis, mitochondrial calcium and caspase 3/7 assays. The study shows that out of the nine compounds used in this study, a tetrahydroquinoline derivative, 2-((1,2,3,4-tetrahydroquinolin-1-yl)(4- methoxyphenyl)methyl) phenol, was found to exhibit strong inhibitory response with IC50 of 50.5 ± 3.8 µM, and therefore can be a potential chemotherapeutic agent. Further experiments revealed that this compound induces cell death by apoptosis and also act as a migration inhibitor. Analysis of the mitochondrial calcium following treatment with the compound on U2OS cells showed a significant reduction in the level of mitochondrial calcium concentration suggesting a mitochondrial calcium-independent mechanism in triggering apoptosis. Treatment of HEK293 cells with the compound confirmed the cytotoxic effects of the compound, however, an increase in the level of mitochondrial calcium was observed. Moreover, the caspase 3/7 mediated cell death was also observed in both cell types.
Conclusion:
Overall, the study suggests that the derivatives of this compound can be used for development of new therapeutics for osteosarcoma and other cancers.
Insights
A novel tetrahydroquinoline derivative shows significant potential as a chemotherapeutic agent for osteosarcoma. This compound effectively inhibits cancer cell growth and migration by inducing apoptosis, offering new therapeutic avenues.
Area of Science:
- Pharmacology
- Biochemistry
- Cancer Research
Background:
- Phenolic compounds exhibit known cytotoxic effects against cancer cells, but their mechanisms remain largely unelucidated.
- Osteosarcoma remains a significant challenge, necessitating the development of novel therapeutic strategies.
Purpose of the Study:
- To evaluate the cytotoxic effects of nine phenol derivatives on human osteosarcoma cells.
- To gain insights into the mechanism of action of these compounds, particularly focusing on apoptosis and migration inhibition.
Main Methods:
- Cytotoxicity was assessed using cell viability assays, scratch assays, DNA content analysis, Annexin V apoptosis assays, and measurements of mitochondrial calcium and caspase 3/7 activity.
- The study utilized human osteosarcoma (U2OS) and human embryonic kidney (HEK293) cell lines.
Main Results:
- A specific tetrahydroquinoline derivative, 2-((1,2,3,4-tetrahydroquinolin-1-yl)(4-methoxyphenyl)methyl) phenol, demonstrated potent cytotoxicity with an IC50 of 50.5 ± 3.8 µM.
- This compound was found to induce apoptosis and inhibit cell migration, with evidence suggesting a mitochondrial calcium-independent pathway in U2OS cells.
- Caspase 3/7 mediated cell death was observed in both U2OS and HEK293 cells, while mitochondrial calcium levels increased in HEK293 cells.
Conclusions:
- The identified tetrahydroquinoline derivative holds promise as a potential chemotherapeutic agent for osteosarcoma.
- Further development of this compound and its derivatives could lead to novel therapeutics for osteosarcoma and other cancers.