Synthesis of Phenol-derivatives and Biological Screening for Anticancer Activity

Title:Synthesis of Phenol-derivatives and Biological Screening for Anticancer Activity

Volume: 17 Issue: 12

Author(s): Anzhelika Karjalainen, Phuong Doan, Jerome G. Chandraseelan, Ossi Sandberg, Olli Yli-Harja , Nuno R. Candeias*Meenakshisundaram Kandhavelu*

Affiliation:

• Dept of Chemistry and Bioengineering, Tampere University of Technology, Korkeakoulunkatu 8, 33101 Tampere,Finland

• Molecular Signaling Lab, Computational Systems Biology Research Group, Department of Signal Processing, Tampere University of Technology, P.O.Box 553, 33101, Tampere,Finland

Keywords: Phenol-derivatives, anticancer, cytotoxicity, cell death, mitochondria, biological screening.

Abstract: 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.

Cite this article as:

Karjalainen Anzhelika , Doan Phuong , Chandraseelan G. Jerome , Sandberg Ossi , Yli-Harja Olli , Candeias R. Nuno*, Kandhavelu Meenakshisundaram*, Synthesis of Phenol-derivatives and Biological Screening for Anticancer Activity, Anti-Cancer Agents in Medicinal Chemistry 2017; 17 (12) . https://dx.doi.org/10.2174/1871520617666170327142027