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Design, synthesis, and molecular docking studies of new [1,2,4]triazolo[4,3-a]quinoxaline derivatives as potential A2B receptor antagonists

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Abstract

Many shreds of evidence have recently correlated A2B receptor antagonism with anticancer activity. Hence, the search for an efficient A2B antagonist may help in the development of a new chemotherapeutic agent. In this article, 23 new derivatives of [1,2,4]triazolo[4,3-a]quinoxaline were designed and synthesized and its structures were confirmed by different spectral data and elemental analyses. The results of cytotoxic evaluation of these compounds showed six promising active derivatives with IC50 values ranging from 1.9 to 6.4 μM on MDA-MB 231 cell line. Additionally, molecular docking for all synthesized compounds was performed to predict their binding affinity toward the homology model of A2B receptor as a proposed mode of their cytotoxic activity. Results of molecular docking were strongly correlated with those of the cytotoxic study. Finally, structure activity relationship analyses of the new compounds were explored.

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Authors and Affiliations

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

    Hany G. Ezzat, Ashraf H. Bayoumi, Farag F. Sherbiny, Ahmed M. El-Morsy, Adel Ghiaty, Mohamed Alswah & Hamada S. Abulkhair

  2. Pharmaceutical Organic Chemistry Department, College of Pharmacy, Misr University for Science and Technology (MUST), 6th October City, Egypt

    Farag F. Sherbiny

  3. Pharmaceutical Chemistry Department, College of Pharmacy, The Islamic University, 54001, Najaf, Iraq

    Ahmed M. El-Morsy

  4. Pharmaceutical Chemistry Department, Faculty of Pharmacy, Horus University - Egypt, International Costal Road, New Damietta, Egypt

    Hamada S. Abulkhair

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  1. Hany G. Ezzat
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  2. Ashraf H. Bayoumi
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Correspondence to Hamada S. Abulkhair.

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Ezzat, H.G., Bayoumi, A.H., Sherbiny, F.F. et al. Design, synthesis, and molecular docking studies of new [1,2,4]triazolo[4,3-a]quinoxaline derivatives as potential A2B receptor antagonists. Mol Divers 25, 291–306 (2021). https://doi.org/10.1007/s11030-020-10070-w

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