1 State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650204, Yunnan, People's Republic of China; 2 Key Laboratory of Bioactive Peptides of Yunnan Province/Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences, Center for Biosafety Mega-Science, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, Yunnan, People's Republic of China; 3 School of Ethnic Medicine, Guizhou Minzu University, Guiyang 550025, Guizhou, People's Republic of China; 4 Institute of Molecular Science, Shanxi University, Taiyuan 030006, Shanxi, People's Republic of China; 5 School of Basic Medical, Kunming Medical University, Kunming 650500, Yunnan, People's Republic of China
Abstract Natural products are the important source for the discovery of more potent anti-HIV agents. In this study, six daphnane diterpenoids including three unreported structures were isolated from Trigonostemon lii, which showed significant activities against HIV-1 strains replication in the nanomolar/picomolar range. Meanwhile, these diterpenoids significantly inhibited the fusion of H9/HIV-1 IIIB cells with uninfected C8166 cells, with the EC50s from 1.06 to 8.73 ng/mL, and did not show any inhibition activities against HIV-1 reverse transcriptase. Moreover, all of the diterpenoids shows significant inhibitions against T20-resistan HIV-1 strains, PNL4-3gp41(36G)V38E, N42S and pNL4-3gp41(36G)V38A, N42T. The results revealed that the six diterpenoids could be a new type of potential lead candidate as an HIV entry inhibitor, particularly for those infected by T20-resistant variants.
Fund:This work was supported financially by grants from the National Science Foundation of China (21432010 and 81660612) and Technological leading talent project of Yunnan (2015HA020). Yunnan Applied Basic Research Project-Kunming Medical University Union Foundation (2017FE467 (-127), Scientific Research Fund Projects from the Department of Education of Yunnan (2016ZDX042) and the HundredTalent Program of Kunming Medical University (60117190441).
Cheng-Jian Tan,Shi-Fei Li,Ning Huang, et al. Daphnane Diterpenoids from Trigonostemon lii and Inhibition Activities Against HIV-1[J]. Natural Products and Bioprospecting,
2020, 10(1): 37-44.