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The role of folic acid in inducing of apoptosis by zinc(II) complex in ovary and cervix cancer cells

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Abstract

Herein, the synthesis, structure, binding affinity, cytotoxicity, and apoptotic properties of the new Zn(II) complex composed of folic acid and bipyridine ligands are reported. Because folic acid has the ability to target cancer cells directly, so it can play a role in targeted drug delivery of the complex and be useful to distinguish normal cells from cancerous. After characterization of Zinc complex utilizing FTIR, EA, and NMR, the results of MTT assay were shown that viability levels of two FR-positive cell lines (HeLa and Ovcar-3) are dependent on time and concentration of [Zn(bpy)FA], whereas, did not show a significant effect on FR-negative cell lines (A549). Also, Real-time PCR revealed that the presence of FA can influence the expression of apoptosis in cervical carcinoma HeLa cells while cisplatin alone doesn't have the ability to trigger apoptosis. Furthermore, the experimental results were evaluated using pharmacophore modeling and molecular docking analysis. Finally, the stability of the Zn(II) complex was surveyed using quantum mechanical studies.

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Acknowledgements

The authors thank the Deputy of Research and Technology of Zabol University of Medical Sciences for all support provided.

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Authors and Affiliations

  1. Department of Gynecology and Obstetrics, Chengdu Second People’s Hospital, Chengdu, Sichuan, 610017, China

    Chuanrong Yu

  2. Department of Medicinal Chemistry, Faculty of Pharmacy, Zabol University of Medical Sciences, Zabol, Iran

    Mostafa Heidari Majd

  3. Department of Chemistry, Faculty of Science, University of Zabol, Zabol, Iran

    Fereshteh Shiri, Somaye Shahraki & Pouya Karimi

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  1. Chuanrong Yu
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Contributions

Chuanrong Yu has contributed to writing, laboratory works, and editing. Mostafa Heidari Majd designed the study and supervised the experiments. Fereshteh Shiri made contributions in conceptualization, visualization, and software. Somaye Shahraki assisted in experimental works, methodology, and validation. Pouya Karimi made contributions in mechanical study. All these authors have substantial contributions to the final manuscript and approved this submission. All authors are aware of the order of authorship and that no further change in authorship will be performed after submission, excepting those previously authorized by the editor-in-chief.

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Correspondence to Mostafa Heidari Majd.

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Ethical statements

This study was approved by the ethical committee of Zabol University of Medical Sciences (IR.ZBMU.REC.1398.209). There is no duplicate publication, fraud, plagiarism, or concerns about animal or human experimentation.

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Yu, C., Heidari Majd, M., Shiri, F. et al. The role of folic acid in inducing of apoptosis by zinc(II) complex in ovary and cervix cancer cells. Mol Divers 26, 1545–1555 (2022). https://doi.org/10.1007/s11030-021-10293-5

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  • DOI: https://doi.org/10.1007/s11030-021-10293-5

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