Synthesis and antiviral activity of formycin derivatives with anti-influenza virus activity
Synthesis and antiviral activity of formycin derivatives with anti-influenza virus activity
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具有抗流感病毒活性的福霉素衍生物的合成及其抗病毒活性
DOI：
10.1016/j.bmc.2022.116613
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发表时间：
2022
影响因子：
3.5
通讯作者：
Takahashi Yoshiaki
中科院分区：
文献类型：
--
作者：
Takada Hisashi;Takizawa Naoki;Shibasaki Shouta;Asaba Hiroki;Igarashi Masayuki;Shibasaki Masakatsu;Takahashi Yoshiaki
在使用我们独特的天然产物库的筛选中，重新发现了具有强抗流感病毒活性的C-核苷抗生素福霉素A。以开发新型抗流感病毒药物为目标，合成了新型的福霉素衍生物，并对其抗流感病毒活性进行了评价。结构修饰主要集中在碱基和糖基两个部分，合成了40多个新的福霉素衍生物。吡唑并嘧啶环的C-7位的修饰强烈地有助于提高活性。特别地，在其中引入杂原子的NHMe（10）、SMe（12）和SeMe（15）衍生物中观察到优异的抗流感病毒活性。此外，在糖部分的修饰中，羟基的存在及其立体化学极大地影响活性的表达和强度。此外，7-SEt衍生物（29）和2′-修饰衍生物（59）的评价结果表明，结构修饰可以降低细胞毒性。
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.