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Synthesis and biological evaluation of prodrugs for nitroreductase based 4-β-amino-4′-Demethylepipodophyllotoxin as potential anticancer agents

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Abstract

A series of prodrugs for nitroreductase (NTR) based 4-β-amino-4′- Demethylepipodophyllotoxin as potential anticancer agents were synthesized, and their antiproliferative activities in vitro showed compounds 2b (IC50 = 0.77, 0.83 and 1.19 μM) and 2d (IC50 = 0.98, 0.91 and 1.58 μM) were greatly selectively toxic to tumor cells A-549, HeLa and HepG2, respectively, and lower damage to normal WI-38 cells in comparison with positive agent Etoposide and Demethylepipodophyllotoxin, and induced cell cycle arrest in the G2/M phase with a concomitant decrease in the population of G1 phase in HeLa cells, which were accompanied by apoptosis. Furthermore, Molecular docking model showed that compounds 2b and 2d appeared to form stable bonds with NTR 1DS7. Taken together, these conjugates have the potential to be developed as antitumor drugs.

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Authors and Affiliations

  1. School of Pharmacy, Lanzhou University, Lanzhou, 730000, PR China

    Zheng-Rong Wu, Wei Deng & Dian He

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  1. Zheng-Rong Wu
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  2. Wei Deng
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  3. Dian He
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Z-RW: software, data curation, writing-original draft. WD: Supervision. DH: funding acquisition, writing—review. Supervision.

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Correspondence to Zheng-Rong Wu or Dian He.

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Wu, ZR., Deng, W. & He, D. Synthesis and biological evaluation of prodrugs for nitroreductase based 4-β-amino-4′-Demethylepipodophyllotoxin as potential anticancer agents. Med Chem Res 31, 1099–1108 (2022). https://doi.org/10.1007/s00044-022-02847-5

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