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Anticancer activities, molecular docking and structure–activity relationship of novel synthesized 4H-chromene, and 5H-chromeno[2,3-d]pyrimidine candidates

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Abstract

In the present study, a series of 4H-chromene and 5H-chromeno[2,3-d]pyrimidine derivatives was synthesized and evaluated as potential cytotoxic agents. The cytotoxic activities of the target compounds were evaluated against four cancer cell lines MCF-7, HCT-116, HepG-2, and A549 in comparison with vinblastine and colchicine as reference drugs. We explored the structure–activity relationship of 4H-chromenes with modification at the 2-,4- or 7-position, and fused pyrimidine ring at 2,3-position. Most of the screened compounds showed marginal antitumor activity against the different cell lines in comparison to the standard drugs. The structure–activity relationship study revealed that the antitumor activity of the synthesized compounds was significantly affected by the lipophilicity of the substituent at the 2-,4- or 7-position for the 4H-chromenes, and 5,8-position or fused pyrimidine ring at 2,3-positions for 5H-chromeno[2,3-d]pyrimidines. Structure–activity relationship was elaborated with the help of molecular docking studies. The structures of the synthesized compounds were established on the basis of the spectral data, infrared, proton nuclear magnetic resonance, 13-Carbon nuclear magnetic resonance and mass spectroscopic data.

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Acknowledgements

The authors deeply thank the RCMP, Al-Azhar University for carrying out the antitumor study and Elemental analyses.

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Authors and Affiliations

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

    Ahmed H. Halawa, Ahmed M. A. I. Abd El-Hady, Hassein A. Emam & Ahmed M. El-Agrody

  2. The Regional Center for Mycology & Biotechnology (RCMP), Al-Azhar University, Nasr City, 11884, Cairo, Egypt

    Mahmoud M. Elaasser

  3. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Cairo University, 11562 Cairo, Egypt

    Ahmed M. El Kerdawy

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  1. Ahmed H. Halawa
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  2. Mahmoud M. Elaasser
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  3. Ahmed M. El Kerdawy
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  4. Ahmed M. A. I. Abd El-Hady
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  6. Ahmed M. El-Agrody
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Correspondence to Ahmed M. El-Agrody.

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Halawa, A.H., Elaasser, M.M., El Kerdawy, A.M. et al. Anticancer activities, molecular docking and structure–activity relationship of novel synthesized 4H-chromene, and 5H-chromeno[2,3-d]pyrimidine candidates. Med Chem Res 26, 2624–2638 (2017). https://doi.org/10.1007/s00044-017-1961-3

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  • DOI: https://doi.org/10.1007/s00044-017-1961-3

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