Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, Fujian 350002, China.
Xiamen Institute of Rare-earth Materials, Chinese Academy of Sciences, Xiamen, Fujian 361021, China.
Curr Pharm Des. 2024;30(18):1398-1403. doi: 10.2174/0113816128282194240329045625.
Influenza virus is a kind of RNA virus. Nowadays, the high incidence of influenza and the morbidity and mortality of epidemic influenza are substantial. It has been reported that one hundred million people in the world are infected with influenza viruses, and two hundred and fifty thousand to five hundred thousand people die from the flu per year. In 2021, the number of infected persons in China was reported to be 654,700, and 0.07% of the infected persons died. The flu has caused a serious threat to human survival. Although several drugs, such as Zanamivir, Oseltamivir, Peramivir, and Laninamivir, have been used in clinics for the treatment of the influenza virus, there are some shortcomings of these drugs. The strain of influenza H5N1 (avian influenza) has been found to resist the effective drug Oseltamivir. Thus, there is an urgent demand to discover new influenza virus inhibitors to overcome the emergence of influenza antigens.
This study aimed to develop new influenza virus inhibitors based on the rupestonic acid parent core.
The rupestonic acid L-ephedrine ester (A) and rupestonic acid L-ephedrine complex (B) were synthesized in this work for the development of influenza virus inhibitors.
The target compounds were synthesized using rupestonic acid and L-ephedrine as starting materials. Their structures were characterized by H NMR and C NMR, and the purity was determined by HPLC. Then, their preliminary influenza activity was evaluated using Oseltamivir as a reference drug.
The results showed that the synthesized rupestonic acid L-ephedrine derivatives A and B were more potent influenza virus inhibitors against the strains of A/PR/8/34 (HN) and A/FM/1/47 (HN) with the IC values of 51.0, 51.0 μM and 441.0, 441.0 μM, respectively, than that of rupestonic acid. By comparing the IC of compounds A and B, compound A can be regarded as a very promising lead compound for the development of influenza virus inhibitors.
The rupestonic acid L-ephedrine ester (A) and rupestonic acid L-ephedrine complex (B) were synthesized and characterized using H NMR and C NMR. Moreover, their purity was determined by HPLC. Both compounds A and B exhibited more potent activities against the strains of A/PR/8/34 (HN) and A/FM/1/47 (HN) than rupestonic acid. Compound A can be regarded as a very promising lead compound for the development of influenza virus inhibitors. Based on these results, more rupestonic acid derivatives will be designed and synthesized in the future for the development of influenza virus inhibitors.
流感病毒是一种 RNA 病毒。如今，流感发病率高，流感流行的发病率和死亡率都很高。据报道，全世界有 1 亿人感染流感病毒，每年有 25 万至 50 万人死于流感。2021 年，中国报告感染人数为 654700 人，感染死亡率为 0.07%。流感病毒对人类的生存造成了严重威胁。尽管扎那米韦、奥司他韦、帕拉米韦和拉尼米韦等几种药物已在临床上用于治疗流感病毒，但这些药物存在一些缺点。已经发现流感 H5N1（禽流感）株对有效药物奥司他韦产生了耐药性。因此，迫切需要发现新的流感病毒抑制剂来克服流感抗原的出现。
本研究旨在以鲁比替康酸母体核心为基础开发新型流感病毒抑制剂。
本工作合成了鲁比替康酸 L-麻黄碱酯（A）和鲁比替康酸 L-麻黄碱复合物（B），用于开发流感病毒抑制剂。
以鲁比替康酸和 L-麻黄碱为起始原料合成目标化合物。通过 1 H NMR 和 13 C NMR 对其结构进行了表征，并通过 HPLC 确定其纯度。然后，以奥司他韦为参比药物，对其初步的流感活性进行了评价。
结果表明，合成的鲁比替康酸 L-麻黄碱衍生物 A 和 B 对 A/PR/8/34（HN）和 A/FM/1/47（HN）株的抑制活性均强于鲁比替康酸，IC 值分别为 51.0、51.0 μM 和 441.0、441.0 μM。通过比较化合物 A 和 B 的 IC 值，可以认为化合物 A 是开发流感病毒抑制剂的很有前途的先导化合物。
采用 1 H NMR 和 13 C NMR 对鲁比替康酸 L-麻黄碱酯（A）和鲁比替康酸 L-麻黄碱复合物（B）进行了合成和表征，并用 HPLC 确定了其纯度。化合物 A 和 B 对 A/PR/8/34（HN）和 A/FM/1/47（HN）株的活性均强于鲁比替康酸。化合物 A 可以被认为是开发流感病毒抑制剂的很有前途的先导化合物。基于这些结果，未来将设计和合成更多的鲁比替康酸衍生物，以开发流感病毒抑制剂。
