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.Graphic
Highlights
According to the latest report on the global AIDS epidemic, infections with the human immunodeficiency virus 1 (HIV1) remain a global threat to public health [1]
Active anti-retroviral therapy has shown significant synergistic effects on prolonging the lifetime and decreasing the mortality of patients, the issues such as toxicity, viral reservoirs and drug resistance have led to a subsequent crisis in the management of HIV/AIDS patients [2]
The above data suggested that compound 1 and the previously identified molecule trigocherriolide B [8, 9] share a similar scaffold, except that one methylene signal at δH 5.17 (s), 5.07 (s) replaced the C-19 methine signal at δH 6.07 (s) in latter
Summary
According to the latest report on the global AIDS epidemic, infections with the human immunodeficiency virus 1 (HIV1) remain a global threat to public health [1]. We reported six daphnane diterpenoids (compounds 1–6) including three unreported ones [trigonolactones B (1), D (2) and E (3)] with significant anti-HIV-1 activity from Trigonostemon lii [7] (Fig. 1) These compounds exhibited strong inhibition on HIV replication with E C50 values of 0.59–8.22 ng/mL and SI values of 1811–29,610, and displayed significantly inhibited the fusion of H9/HIV1IIIB cells with uninfected C8166 cells with EC50 values of 1.06–8.73 ng/mL, while did not show any inhibition activity against HIV-1 reverse transcriptase. More important, these compounds still displayed significant inhibitions against T20-resistant HIV-1 strains, pNL4-3gp41(36G)V38E, N42S and pNL4-3gp41(36G)V38A, N42T. The structures of these compounds were established by spectroscopic approach including 1D, 2D NMR and HRMS technology
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
