Affiliation:
1. Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, Fujian 350002, China
2. Xiamen Institute
of Rare-earth Materials, Chinese Academy of Sciences, Xiamen, Fujian 361021, China
Abstract
Background:
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.
Aims:
This study aimed to develop new influenza virus inhibitors based on the rupestonic acid parent core.
Objective:
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.
Methods:
The target compounds were synthesized using rupestonic acid and L-ephedrine as starting materials.
Their structures were characterized by 1H NMR and 13C NMR, and the purity was determined by HPLC. Then,
their preliminary in vitro influenza activity was evaluated using Oseltamivir as a reference drug.
Results:
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 (H1N1) and A/FM/1/47 (H1N1) with the IC50
values of 51.0, 51.0 μM and 441.0, 441.0 μM, respectively, than that of rupestonic acid. By comparing the IC50
of compounds A and B, compound A can be regarded as a very promising lead compound for the development
of influenza virus inhibitors.
Conclusion:
The rupestonic acid L-ephedrine ester (A) and rupestonic acid L-ephedrine complex (B) were synthesized
and characterized using 1H NMR and 13C 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 (H1N1) and
A/FM/1/47 (H1N1) 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.
Funder
National Natural Science Foundation of China
Science and Technology Planning Program of Xiamen
Publisher
Bentham Science Publishers Ltd.
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