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Aryl azide-sulfonamide hybrids induce cellular apoptosis: synthesis and preliminary screening of their cytotoxicity in human HCT116 and A549 cancer cell lines

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Abstract

Simple, small, drug-like molecules bearing aryl azide and aryl sulfonamide moieties were designed and synthesized. The cytotoxic activity of these compounds was measured on colon cancer HCT116, lung cancer A549, and normal fibroblast cells F180 cell lines. All the synthesized compounds showed a significant cytotoxic activity below 100 µM in both HCT116 and A549 cells. Compounds 10e and 10f exhibited the most potent activity with IC50 values of 2.20 and 6.27 µM on A549 and HCT116 cells, respectively. Also, compounds 10e and 10f showed significant tumor selectivity on HCT116 and A549 cell lines when compared with the reference cytotoxic agent staurosporine. This indicated the promising safety of these compounds on normal cells. In addition, flow cytometry studies showed that HCT116 cell lines treated with the most active compound 10f were arrested in the G2/M phase of the cell cycle. 10f boosted both early and late apoptosis at HCT116 cells. A hypothetical pharmacophore model was built using 14 reported potent carbonic anhydrase I inhibitors. The pharmacophoric study revealed that the tested sulfonamide derivatives 10e and 10f showed significant fitting on the pharmacophore query with reasonable RMSD values. Molecular docking study showed a chelation reaction with the key Zn atom, in addition to different hydrogen bonding, and van der Waals interactions with several important amino acids inside the CA Ι active site.

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Acknowledgements

The authors extend their appreciation to faculty of Pharmacy, the British University in Egypt and the Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Assiut University for their support to synthesis these azide-sulfonamides and perform the preliminary cytotoxic studies. Special thanks to Assoc. Prof. Ahmed S. Aboraia for helping in performing the pharmacophoric study.

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Authors and Affiliations

  1. Student Research Center, Faculty of Pharmacy, Assiut University, Assiut, 71515, Egypt

    Ahmed El-Kardocy

  2. Pharmaceutical Chemistry Department, Faculty of Pharmacy, Deraya University, Minya, Egypt

    Muhamad Mustafa

  3. VACSERA, Cairo, Egypt

    Esam R. Ahmed

  4. Faculty of Pharmacy, The British University in Egypt, Cairo-Suez Desert Road, Al-Sherouk, 11837, Egypt

    Samy Mohamady

  5. Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Assiut University, Assiut, 71526, Egypt

    Yaser A. Mostafa

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  1. Ahmed El-Kardocy
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  2. Muhamad Mustafa
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  3. Esam R. Ahmed
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  5. Yaser A. Mostafa
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Correspondence to Yaser A. Mostafa.

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El-Kardocy, A., Mustafa, M., Ahmed, E.R. et al. Aryl azide-sulfonamide hybrids induce cellular apoptosis: synthesis and preliminary screening of their cytotoxicity in human HCT116 and A549 cancer cell lines. Med Chem Res 28, 2088–2098 (2019). https://doi.org/10.1007/s00044-019-02438-x

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