DataSheet1_Discovery of Novel α-Aminophosphonates with Hydrazone as Potential Antiviral Agents Combined With Active Fragment and Molecular Docking.docx

A series of novel α-aminophosphonate derivatives containing hydrazone were designed and synthesized based on active fragments. Bioassay results demonstrated that title compounds possessed good activities against tobacco mosaic virus. Among them, compounds 6a, 6g, 6i, and 6j were equivalent to the commercial antiviral agents like dufulin. On structure optimization-based molecular docking, compound 6k was synthesized and displayed excellent activity with values of 65.1% curative activity, 74.3% protective activity, and 94.3% inactivation activity, which were significantly superior to the commercial antiviral agents dufulin and ningnanmycin. Therefore, this study indicated that new lead compounds could be developed by adopting a joint strategy with active fragments and molecular docking.

基于活性片段设计并合成了系列新颖的α-氨基膦酸酯衍生物，其中含有腙结构。生物活性测试结果表明，所述化合物对烟草花叶病毒表现出良好的活性。其中，化合物6a、6g、6i和6j的活性与市售抗病毒剂如多福林相当。在结构优化和分子对接的基础上，合成了化合物6k，并显示出卓越的活性，其治愈率为65.1%，防护率为74.3%，灭活率为94.3%，均显著优于市售抗病毒剂多福林和宁南霉素。因此，本研究表明，通过结合活性片段和分子对接的联合策略，可以开发新的先导化合物。