ArticleMolecular pharmacology2011
Iron chelators of the di-2-pyridylketone thiosemicarbazone and 2-benzoylpyridine thiosemicarbazone series inhibit HIV-1 transcription: identification of novel cellular targets--iron, cyclin-dependent kinase (CDK) 2, and CDK9.
Article in Molecular pharmacology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 68 citations in OpenAlex.
- Small Molecule Regulation of Iron Homeostasis: Design and Optimization of Novel Iron Chelators Based on a Thiosemicarbazone Scaffold.Journal of molecular structure · 2025Article
- A DFT study on the heterolytic bond cleavage of hydrazones under cathodic conditions in acetonitrile.Journal of molecular modeling · 2024Article
- HIV-1 infection in sickle cell disease and sickle cell trait: role of iron and innate response.Expert review of hematology · 2022Article
- Disrupting the Cdk9/Cyclin T1 heterodimer of 7SK snRNP for the Brd4 and AFF1/4 guided reconstitution of active P-TEFb.Nucleic acids research · 2022Article
- Restriction of HIV-1 infection in sickle cell trait.Blood advances · 2021Article
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- Air pollutants disrupt iron homeostasis to impact oxidant generation, biological effects, and tissue injury.Free radical biology & medicine · 2020Review
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- Depriving Iron Supply to the Virus Represents a Promising Adjuvant Therapeutic Against Viral Survival.Current clinical microbiology reports · 2020Review
- Iron intake is positively associated with viral load in antiretroviral naïve Brazilian men living with HIV.Memorias do Instituto Oswaldo Cruz · 2020Observational
- Specific ActivationJournal of virology · 2019Article
- HIV-1 Tat phosphorylation on Ser-16 residue modulates HIV-1 transcription.Retrovirology · 2018Article
- Inhibition of HIV-1 infection in humanized mice and metabolic stability of protein phosphatase-1-targeting small molecule 1E7-03.Oncotarget · 2017Article
- Iron overload down-regulates the expression of the HIV-1 Rev cofactor eIF5A in infected T lymphocytes.Proteome science · 2017Article
- Protein Phosphatase-1 -targeted Small Molecules, Iron Chelators and Curcumin Analogs as HIV-1 Antivirals.Current pharmaceutical design · 2017Review
- Increased iron export by ferroportin induces restriction of HIV-1 infection in sickle cell disease.Blood advances · 2016Article
- Alkaloids from the Sponge Stylissa carteri Present Prospective Scaffolds for the Inhibition of Human Immunodeficiency Virus 1 (HIV-1).Marine drugs · 2016Article
- Investigation of the salicylaldehyde thiosemicarbazone scaffold for inhibition of influenza virus PA endonuclease.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2015Article
- Reactivation of latent HIV-1 provirus via targeting protein phosphatase-1.Retrovirology · 2015Article
- Discovery of novel 5-fluoro-MedChemComm · 2015Article
Corrections and comments
- Erratum issuedKarla, Pradeep K [removed]
Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
HIV-1 transcription is activated by HIV-1 Tat protein, which recruits cyclin-dependent kinase 9 (CDK9)/cyclin T1 and other host transcriptional coactivators to the HIV-1 promoter. Tat itself is phosphorylated by CDK2, and inhibition of CDK2 by small interfering RNA, the iron chelator 2-hydroxy-1-naphthylaldehyde isonicotinoyl hydrazone (311), and the iron chelator deferasirox (ICL670) inhibits HIV-1 transcription. Here we have analyzed a group of novel di-2-pyridylketone thiosemicarbazone- and 2-benzoylpyridine thiosemicarbazone-based iron chelators that exhibit marked anticancer activity in vitro and in vivo (Proc Natl Acad Sci USA 103:7670-7675, 2006; J Med Chem 50:3716-3729, 2007). Several of these iron chelators, in particular 2-benzoylpyridine 4-allyl-3-thiosemicarbazone (Bp4aT) and 2-benzoylpyridine 4-ethyl-3-thiosemicarbazone (Bp4eT), inhibited HIV-1 transcription and replication at much lower concentrations than did 311 and ICL670. Neither Bp4aT nor Bp4eT were toxic after a 24-h incubation. However, longer incubations for 48 h or 72 h resulted in cytotoxicity. Analysis of the molecular mechanism of HIV-1 inhibition showed that the novel iron chelators inhibited basal HIV-1 transcription, but not the nuclear factor-κB-dependent transcription or transcription from an HIV-1 promoter with inactivated SP1 sites. The chelators inhibited the activities of CDK2 and CDK9/cyclin T1, suggesting that inhibition of CDK9 may contribute to the inhibition of HIV-1 transcription. Our study suggests the potential usefulness of Bp4aT or Bp4eT in antiretroviral regimens, particularly where resistance to standard treatment occurs.
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