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In vitro antitumor evaluation of 4H-chromene-3-carbonitrile derivatives as a new series of apoptotic inducers

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Tumor Biology

Abstract

Apoptosis is a naturally occurring process by which a cell is directed to programmed cell death. Chemotherapy drugs affect the cancer cells by the apoptotic induction. During the present study, a series of 4H-chromene-3-carbonitrile was synthesized by one-pot method as the inducers of apoptosis. Cytotoxic effects of six compounds of 4H-chromene-3-carbonitrile were evaluated against five tumor cell lines, with the help of colorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Compound 4 showed significant cytotoxic activity and was selected for conjugation with the synthesized gold nanoparticles by aspartic acid. Also, we evaluated apoptosis induction capacity of the selected compound with the help of fluorescent dyes and DNA fragmentation. The result showed that the conjugated and non-conjugated forms of compound 4 were effective in inducing apoptosis and conjugated one had more efficiency and reduced the effective dose. Also, molecular modeling experiments involving compound 4 and colchicine binding site of tubulin dimer showed several strong hydrogen bonds and hydrophobic interactions to many important amino acid residues and GTP.

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Acknowledgments

We thank Dr. Amaneh Javid for the critical reading of manuscript. This work was supported by a grant from Science and Research Branch, Islamic Azad University, Kurdistan, Iran. We are grateful for the help provided by the Department of Pilot Nanobiotechnology, Pasteur Institute, Tehran, Iran.

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Authors and Affiliations

  1. Department of Pilot Nanobiotechnology, Pasteur Institute of Iran, Tehran, Iran

    Zahra Saffari, Azim Akbarzadeh, Maryam Farahnak Zarabi & Ali Farhangi

  2. Department of Biochemistry, Science and Research Branch, Islamic Azad University, Kurdistan, Iran

    Zahra Saffari

  3. Department of Biology, Faculty of Science, Golestan University, Gorgan, Iran

    Hassan Aryapour

  4. Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran

    Alireza Foroumadi & Najmeh Jafari

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  1. Zahra Saffari
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  2. Hassan Aryapour
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Correspondence to Hassan Aryapour or Azim Akbarzadeh.

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Saffari, Z., Aryapour, H., Akbarzadeh, A. et al. In vitro antitumor evaluation of 4H-chromene-3-carbonitrile derivatives as a new series of apoptotic inducers. Tumor Biol. 35, 5845–5855 (2014). https://doi.org/10.1007/s13277-014-1775-6

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  • DOI: https://doi.org/10.1007/s13277-014-1775-6

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