ArticlePloS one2014
Dual role of novel ingenol derivatives from Euphorbia tirucalli in HIV replication: inhibition of de novo infection and activation of viral LTR.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 87 citations in OpenAlex.
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- Discovery of HIV entry inhibitors via a hybrid CXCR4 and CCR5 receptor pharmacophore-based virtual screening approach.European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences · 2020Article
- Bioactive diterpenoid metabolism and cytotoxic activities of genetically transformed Euphorbia lathyris roots.Phytochemistry · 2020Article
- Anti-HIV tigliane diterpenoids from Reutealis trisperma.Phytochemistry · 2020Article
- Brain macrophages harbor latent, infectious simian immunodeficiency virus.AIDS (London, England) · 2019Review
- Semi-Synthetic Ingenol Derivative from Euphorbia tirucalli Inhibits Protein Kinase C Isotypes and Promotes Autophagy and S-phase Arrest on Glioma Cell Lines.Molecules (Basel, Switzerland) · 2019Article
- Modified ingenol semi-synthetic derivatives from Euphorbia tirucalli induce cytotoxicity on a large panel of human cancer cell lines.Investigational new drugs · 2019Article
- Antiretroviral treatment, government policy and economy of HIV/AIDS in Brazil: is it time for HIV cure in the country?AIDS research and therapy · 2019Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
HIV infection is not cleared by antiretroviral drugs due to the presence of latently infected cells that are not eliminated with current therapies and persist in the blood and organs of infected patients. New compounds to activate these latent reservoirs have been evaluated so that, along with HAART, they can be used to activate latent virus and eliminate the latently infected cells resulting in eradication of viral infection. Here we describe three novel diterpenes isolated from the sap of Euphorbia tirucalli, a tropical shrub. These molecules, identified as ingenols, were modified at carbon 3 and termed ingenol synthetic derivatives (ISD). They activated the HIV-LTR in reporter cell lines and human PBMCs with latent virus in concentrations as low as 10 nM. ISDs were also able to inhibit the replication of HIV-1 subtype B and C in MT-4 cells and human PBMCs at concentrations of EC50 0.02 and 0.09 µM respectively, which are comparable to the EC50 of some antiretroviral currently used in AIDS treatment. Control of viral replication may be caused by downregulation of surface CD4, CCR5 and CXCR4 observed after ISD treatment in vitro. These compounds appear to be less cytotoxic than other diterpenes such as PMA and prostratin, with effective dose versus toxic dose TI>400. Although the mechanisms of action of the three ISDs are primarily attributed to the PKC pathway, downregulation of surface receptors and stimulation of the viral LTR might be differentially modulated by different PKC isoforms.
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