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In vitro anticancer activity of pyrano[3, 2-c]chromene derivatives with both cell cycle arrest and apoptosis induction

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Abstract

A series of 2-amino-4-aryl-5-oxo-4,5-dihydropyrano[3,2-c]chromene-3-carbonitrile (4a–m) were synthesized via a one-pot three component condensation reaction between 4-hydroxy-2H-chromen-2-one, various aryl aldehydes and malononitrile in the presence of piperidine as a catalyst in ethanol under microwave irradiation conditions, with good to excellent yields. The structure elucidations of all the synthesized compounds were accomplished by spectral data, IR, 1H NMR, 13C NMR, MS, and elemental analyses. The targeted compounds were assessed for their in vitro anticancer activity against mammary gland breast cancer cell line (MCF-7), human colon cancer (HCT-116), and liver cancer (HepG-2) by using sulphorhodamine B assay (SRB) method, while doxorubicin, was utilized as standard reference drug. The cancer cells were treated with the synthesized compounds at differentiable dosages, and cell viability was determined. Compounds 4e, 4f, and 4m exhibited excellent antitumor activity versus all cancer cell lines with IC50 values ranging from 0.2 to 1.7 μM. The cell cycle arrest behavior of compounds 4e, 4f, and 4m was investigated. The results illustrated that the potent cytotoxic compounds 4e, 4f, and 4m induce cell cycle arrest at the G2/M phases and trigger apoptosis in the different tested cancer cells. Finally, the structure activity relationship (SAR) survey highlighted the antitumor activity of the new molecules that was remarkably influenced by the hydrophilicity of certain substituents at certain positions.

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Acknowledgements

The authors extend their appreciation to the Deanship of Science Research at King Khalid University for funding this work through General Research Project under Grant Number (R.G.P.1/111/40). In addition, the authors deeply thank the Regional Center for Mycology & Biotechnology (RCMP), Al-Azhar University, Cairo, Egypt, for carrying out the antitumor study, elemental analyses and also, for Mr. Ali Y. A. Alshahrani for drawing the 1H NMR and 13C NMR spectra.

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Authors and Affiliations

  1. Chemistry Department, Faculty of Science, Al-Azhar University, Nasr City, 11884, Cairo, Egypt

    Ahmed M. El-Agrody & Ahmed Mora

  2. Chemistry Department, Faculty of Science, King Khalid University, Abha, 61413, Saudi Arabia

    Ahmed M. Fouda, Mohammed A. Assiri, Tarik E. Ali & Mohammed M. Alam

  3. Department of Chemistry, Faculty of Education, Ain Shams University, Roxy, Cairo, Egypt

    Tarik E. Ali

  4. Bioloogy Department, Faculty of Science, King Khalid University, Abha, 61413, Saudi Arabia

    Mohammad Y. Alfaifi

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  1. Ahmed M. El-Agrody
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  4. Ahmed Mora
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El-Agrody, A.M., Fouda, A.M., Assiri, M.A. et al. In vitro anticancer activity of pyrano[3, 2-c]chromene derivatives with both cell cycle arrest and apoptosis induction. Med Chem Res 29, 617–629 (2020). https://doi.org/10.1007/s00044-019-02494-3

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