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Inducing apoptosis through upregulation of p53: structure–activity exploration of anthraquinone analogs

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Abstract

We previously reported a series of p53-elevating anthraquinone compounds with considerable cytotoxicity for acute lymphoblastic leukemia (ALL) cells. To further develop this class of compounds, we examined the effect of a few key structural features on the anticancer structure–activity relationship (SAR) in ALL cells. The active analogs showed comparable cytotoxicity and upregulation of p53 but did not induce significant downregulation of MDM2 as seen with the lead compound AQ-101, indicating the importance of the anthraquinone core scaffold for MDM2 regulation. The result from the current study not only contributes to the SAR framework of these anthraquinone derivatives but also opens up new chemical space for further optimization work.

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Acknowledgements

Financial support from the National Institutes of Health (CA180519) is gratefully acknowledged. We also thank the Center for Diagnostics and Therapeutics for a University fellowship to AA, the Georgia Research Alliance for an Eminent Scholar endowment, and GSU internal support.

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Author notes

  1. These authors contributed equally: A. Anifowose, A. A. Agbowuro

Authors and Affiliations

  1. Department of Chemistry and Center for Diagnostics and Therapeutics, Petit Science Center, Georgia State University, 100 Piedmont Ave, Atlanta, GA, 30303, USA

    Abiodun Anifowose, Ayodeji A. Agbowuro, Ravi Tripathi, Wen Lu, Xiaoxiao Yang & Binghe Wang

  2. Department of Pharmaceutical Sciences, College of Pharmacy, University of Mississippi, Oxford, MS, USA

    Chalet Tan

Authors
  1. Abiodun Anifowose
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  2. Ayodeji A. Agbowuro
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  3. Ravi Tripathi
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  4. Wen Lu
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  5. Chalet Tan
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  6. Xiaoxiao Yang
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  7. Binghe Wang
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Corresponding authors

Correspondence to Xiaoxiao Yang or Binghe Wang.

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The authors declare that they have no conflict of interest.

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Dedicated to Professor Robert P. Hanzlik on the occasion of his retirement after 49 years of service on the faculty of the Department of Medicinal Chemistry, University of Kansas.

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Anifowose, A., Agbowuro, A.A., Tripathi, R. et al. Inducing apoptosis through upregulation of p53: structure–activity exploration of anthraquinone analogs. Med Chem Res 29, 1199–1210 (2020). https://doi.org/10.1007/s00044-020-02563-y

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