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Inhibition of human parainfluenza virus type 1 sialidase by analogs of 2-deoxy-2,3-didehydro-N-acetylneuraminic acid

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Abstract

Eleven novel analogs of 2-deoxy-2,3-didehydro-N-acetylneuraminic acid (Neu5Ac2en) modified at the C-4 and C-9 positions were designed and tested for their ability to inhibit sialidase of human parainfluenza virus type 1 (hPIV-1). The analogs modified by the cyanomethyl, amidinomethyl, and thiocarbamoylmethyl groups at the C-4 position exhibited potent inhibition against hPIV-1 sialidase compared with Neu5Ac2en. The most effective compound was thiocarbamoylmethyl analog (4-O-thiocarbamoylmethyl-Neu5Ac2en). The activity of 4-O-thiocarbamoylmethyl-Neu5Ac2en causing 50% enzyme inhibition at a concentration of approximately 1.0×10−5M was 30-fold larger than Neu5Ac2en. While, the analogs of Neu5Ac2en modified by the azido and N-acetyl groups at the C-9 showed a decrease in inhibition of sialidase compared with the 9-hydroxy analogs. In addition, 4-O-thiocarbamoylmethyl-Neu5Ac2en strongly inhibited hPIV-1 infections of Lewis lung carcinoma-monkey kidney cells in comparison with Neu5Ac2en. The present findings would provide useful information for the development of anti-human parainfluenza virus compounds.

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Authors and Affiliations

  1. Department of Biochemistry, University of Shizuoka, School of Pharmaceutical Sciences, Shizuoka, 422-8526, Japan

    Takashi Suzuki, Noriko Koyama, Chika Hosokawa, Toshihiro Kogure, Tadanobu Takahashi, Kazuya I.-P. Jwa Hidari, Daisei Miyamoto & Yasuo Suzuki

  2. Department of Organic Chemistry, University of Shizuoka, School of Pharmaceutical Sciences, Shizuoka, 422-8526, Japan

    Kiyoshi Ikeda

  3. Department of Synthetic Organic and Medicinal Chemistry, University of Shizuoka, School of Pharmaceutical Sciences, Shizuoka, 422-8526, Japan

    Kiyoshi Tanaka

Authors
  1. Takashi Suzuki
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  2. Kiyoshi Ikeda
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  3. Noriko Koyama
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  4. Chika Hosokawa
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  5. Toshihiro Kogure
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  6. Tadanobu Takahashi
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  7. Kazuya I.-P. Jwa Hidari
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  9. Kiyoshi Tanaka
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  10. Yasuo Suzuki
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Suzuki, T., Ikeda, K., Koyama, N. et al. Inhibition of human parainfluenza virus type 1 sialidase by analogs of 2-deoxy-2,3-didehydro-N-acetylneuraminic acid. Glycoconj J 18, 331–337 (2001). https://doi.org/10.1023/A:1013617232576

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  • DOI: https://doi.org/10.1023/A:1013617232576

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