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Synthesis and biological evaluation of novel naphthoquinone fused cyclic aminoalkylphosphonates and aminoalkylphosphonic monoester

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Summary.

A series of novel naphthoquinone fused cyclic α-aminophosphonates, 2-alkoxy-3,4-dihydro-2H-naphtho[2,3-e][1,4,2]oxazaphosphinane-5,10-dione 2-oxide 3–17 and naphthoquinone fused cyclic α-aminophosphonic monoester 18 were synthesized for the first time. These cyclic α-aminophosphonates were evaluated for antitumor activity on four human tumor cell lines, and three of them showed significant cytotoxicity (IC50: 0.019–5.15 µM) comparable to that of the reference drug doxorubicin. Furthermore, inhibition assays for topoisomerase II-mediated relaxation of supercoiled DNA indicated that the naphthoquinone fused cyclic aminophosphonates were catalytic inhibitors of topoisomerase II.

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Authors and Affiliations

  1. College of Pharmaceutical Sciences, Nankai University, Tianjin, China

    B. Wang

  2. State Key Laboratory and Institute of Elemento-Organic Chemistry, Nankai University, Tianjin, China

    B. Wang, Z. W. Miao & R. Y. Chen

  3. Tianjin Institute of Medical and Pharmaceutical Sciences, Tianjin, China

    J. Wang

  4. Tianjin Key Laboratory of Microbial Functional Genomics, Department of Cancer Research, College of Life Science, Institute for Molecular Biology, Nankai University, Tianjin, China

    X. D. Zhang

Authors
  1. B. Wang
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  2. Z. W. Miao
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  3. J. Wang
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  4. R. Y. Chen
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  5. X. D. Zhang
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Additional information

Authors’ address: Prof. Bin Wang, College of Pharmaceutical Sciences, Nankai University, Tianjin 300071, China

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Wang, B., Miao, Z., Wang, J. et al. Synthesis and biological evaluation of novel naphthoquinone fused cyclic aminoalkylphosphonates and aminoalkylphosphonic monoester. Amino Acids 35, 463–468 (2008). https://doi.org/10.1007/s00726-007-0570-8

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  • DOI: https://doi.org/10.1007/s00726-007-0570-8

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