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In vitro evaluation of the anticancer activity of barbituric/thiobarbituric acid-based chromene derivatives

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Abstract

Background

Cancer is one of the most important reasons for mortality worldwide. Several synthetic products have shown valuable efficiency as an anticancer medicines. Chromene derivatives have long been used as the promising compounds which are potent in inhibition of the growth of tumors.

Methods and results

In this study, we investigate an anticancer activity of barbituric/thiobarbituric acid-based chromene derivates. For this purpose, viability, antioxidant and apoptotic assays were conducted using three different cancer cell lines (A2780, MCF7, and A549). In most cases, the antiproliferative activity of barbituric acid-based derivatives was higher than that of thiobarbituric acid-based compounds. Among 14 compounds, compound 4g was the most potent one, which showed the highest effect on cells by increasing the accumulation of ROS (up to 540% increase), increasing the level of caspase-3 and caspase-9 (~ 35% increase), and decreasing the mitochondrial membrane potential (2.5 folds reduction). To characterize the type of cell death involved into our experiment Annexin V/PI double staining of compound 4g was performed. The results showed that the number of late apoptotic and/or necrotic cells (Ann V + /PI +) increased fourfold upon treatment with IC50 concentration of 4g.

Conclusions

Overall, the anti-proliferative activity of barbituric acid-based derivatives was higher than that of thiobarbituric acid compounds, and compound 4g can be introduced as a potential candidate to prevent various cancers.

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Data availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

The authors gratefully acknowledge the Research Council of Kermanshah University of Medical Sciences (Grant No. 980442) and Alzahra Uiversity for the financial support.

Funding

The research leading to these results received funding from Kermanshah University of Medical Sciences (KUMS) under Grant Agreement No. 980422.

Author information

Authors and Affiliations

  1. Department of Biotechnology, Faculty of Biological Sciences, Alzahra University, Tehran, Iran

    Seyyed Abolghasem Ghadami

  2. Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, 67145-1673, Kermanshah, IR, Iran

    Leila Hosseinzadeh, Nasrin Yarmohammadi & Hadi Adibi

  3. Student Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran

    Ehsan Eskandari

Authors
  1. Seyyed Abolghasem Ghadami
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  2. Leila Hosseinzadeh
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  4. Nasrin Yarmohammadi
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  5. Hadi Adibi
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Contributions

S.A.G., and H.A. designed research; L.H., and H.A. synthesize the compounds; S.A.G., E.E., and L.H. performed research; L.H., and N.Y. performed cell study; S.A.G., L.H., E.E., and H.A. analyzed data; and S.A.G., L.H., and H.A. wrote the paper. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Hadi Adibi.

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Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of Kermanshah University of Medical Sciences under code No. IR.KUMS.REC.1398.463.

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Ghadami, S.A., Hosseinzadeh, L., Eskandari, E. et al. In vitro evaluation of the anticancer activity of barbituric/thiobarbituric acid-based chromene derivatives. Mol Biol Rep 48, 7637–7646 (2021). https://doi.org/10.1007/s11033-021-06738-7

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  • DOI: https://doi.org/10.1007/s11033-021-06738-7

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