2. Academic Validation
  3. Synthesis and antiviral activity of formycin derivatives with anti-influenza virus activity

Synthesis and antiviral activity of formycin derivatives with anti-influenza virus activity

  • Bioorg Med Chem. 2022 Mar 1:57:116613. doi: 10.1016/j.bmc.2022.116613.
Hisashi Takada 1,  Naoki Takizawa 2,  Shouta Shibasaki 2,  Hiroki Asaba 2,  Masayuki Igarashi 2,  Masakatsu Shibasaki 2,  Yoshiaki Takahashi 3
Affiliations

Affiliations

  • 1 Institute of Microbial Chemistry (BIKAKEN), 3-14-23 Kamiosaki, Shinagawa-ku, Tokyo 141-0021, Japan. Electronic address: takadah@bikaken.or.jp.
  • 2 Institute of Microbial Chemistry (BIKAKEN), 3-14-23 Kamiosaki, Shinagawa-ku, Tokyo 141-0021, Japan.
  • 3 Institute of Microbial Chemistry (BIKAKEN), 3-14-23 Kamiosaki, Shinagawa-ku, Tokyo 141-0021, Japan. Electronic address: takashow@bikaken.or.jp.
PMID: 35092894 DOI: 10.1016/j.bmc.2022.116613
Abstract

In a screening using our unique natural product library, the C-nucleoside Antibiotic formycin A, which exerts strong anti-influenza virus activity, was rediscovered. Aiming to develop a new type of anti-influenza virus drug, we synthesized new derivatives of formycin and evaluated its anti-influenza virus activity. Structural modifications were focused on the base moiety and sugar portion, respectively, and >40 novel formycin derivatives were synthesized. Modification of the C-7 position of the pyrazolopyrimidine ring strongly contributed to improve the activity. In particular, excellent anti-influenza virus activity was observed in the NHMe (10), SMe (12), and SeMe (15) derivatives, in which heteroatoms were introduced. In addition, in the modification of the sugar moiety, the presence of a hydroxyl group and its stereochemistry greatly affected both the expression and intensity of the activity. Furthermore, the evaluation results of the 7-SEt derivative (29) and the 2'-modified derivative (59) suggested that structural modifications may reduce cytotoxicity.

Keywords

Anti-influenza virus drugs; Formycin derivatives; Natural product; Structure-activity relationships.

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