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Exploration of quinolone and quinoline derivatives as potential anticancer agents

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DARU Journal of Pharmaceutical Sciences Aims and scope Submit manuscript

Abstract

Background

Among the different types of cancers, breast cancer, bone cancer and cervical cancer are the most common gender specific cancer types that are affecting the women worldwide. Currently, many enzymatic and cellular pathways are known as drug targets for the treatment of cancer. Even though many improvements have been made in the therapy of various types of cancer, but the major disadvantage of available anti-cancer drugs is their non-selective behavior towards cancer cells as well as normal cells.

Objectives

In the light of this fact, the searching of new compounds with selective behavior only towards cancer cells is critically important. Previously, we have identified several series of compounds as the potential inhibitors of these families.

Methods

Herein, we investigate quinolones and quinolines for their anti-cancer activity against breast cancer cells (MCF–7), bone marrow cancer cells (K–562) and cervical cancer cells (HeLa) by MTT assay. The most effective derivatives were further subjected to flow cytometry analysis followed by fluorescence microscopic analysis by using 4´,6-diamidine-2´-phenylindole (DAPI) and propidium staining (PI) staining.

Results

All the tested compounds were found selective only towards cancer cells. The identified compounds also induced either G2 or S-phase cell cycle arrest within the respective cancer cell line, chromatin condensation and the nuclear fragmentation, as well as maximum interaction with DNA.

Conclusions

These results provide evidence that the characteristic chemical features of attached groups are the key factors for their anticancer effects and play a useful role in revealing the mechanisms of action in relation to the known compounds in future research programs.

Flow cytometric analysis of cell cycle using propidium iodide staining. Cell apoptosis observed under fluorescence microscope using DAPI and PI staining.

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Acknowledgements

J.I. is thankful to the Higher Education Commission of Pakistan for the financial support through Project No.Ph-V-MG-3/Peridot/R&D/HEC/2019 and 6927/NRPU/R&D/17.

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Authors and Affiliations

  1. Centre for Advanced Drug Research, COMSATS University Islamabad, Abbottabad Campus, Abbottabad, 22060, Pakistan

    Jamshed Iqbal & Syeda Abida Ejaz

  2. Department of Chemistry, Quaid-i-Azam University, -45320, Islamabad, Pakistan

    Imtiaz Khan

  3. Institut für Chemie, Universität Rostock, Albert Einstein Str. 3a, 18059, Rostock, Germany

    Elina Ausekle, Mariia Miliutina & Peter Langer

  4. Institut für Chemie, Universität Rostock, Albert Einstein Str. 3a, 18059, Rostock, Germany

    Peter Langer

Authors
  1. Jamshed Iqbal
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  2. Syeda Abida Ejaz
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  3. Imtiaz Khan
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  4. Elina Ausekle
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  5. Mariia Miliutina
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  6. Peter Langer
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Contributions

Syeda Abida Ejaz performed the biochemical assays and drafted the manuscript under the supervision of Jamshed Iqbal. Imtiaz Khan, Elina Ausekle, Mariia Miliutina and Peter Langer provided the compounds for the study. All the authors checked and finally approved the draft before submission.

Corresponding author

Correspondence to Jamshed Iqbal.

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The authors confirm that this article content has no conflict of interest. The authors also declare no competing financial interests.

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Iqbal, J., Ejaz, S.A., Khan, I. et al. Exploration of quinolone and quinoline derivatives as potential anticancer agents. DARU J Pharm Sci 27, 613–626 (2019). https://doi.org/10.1007/s40199-019-00290-3

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  • DOI: https://doi.org/10.1007/s40199-019-00290-3

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