ArticleJournal of medicinal chemistry2013
Exploiting drug-resistant enzymes as tools to identify thienopyrimidinone inhibitors of human immunodeficiency virus reverse transcriptase-associated ribonuclease H.
Article in Journal of medicinal chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 41 citations in OpenAlex.
- Ligand‑Based Virtual Screening Discovery of Thienopyrimidinone Derivatives as Allosteric nSMase2 Modulators and Antivirals Against West Nile Virus.ChemMedChem · 2026Article
- 2-(Trihydroxyphenyl)thienopyrimidinones as Key Scaffolds for Targeting a Novel Allosteric Site of HIV-1 Integrase.Molecules (Basel, Switzerland) · 2025Article
- Article
- Magic shotgun approach to anti-inflammatory pharmacotherapy: Synthesis of novel thienopyrimidine monomers/heterodimer as dual COX-2 and 15-LOX inhibitors endowed with potent antioxidant activity.European journal of medicinal chemistry · 2023Article
- Targeting Ribonucleases with Small Molecules and Bifunctional Molecules.ACS chemical biology · 2023Review
- Dihydroxyphenyl- and Heteroaromatic-Based Thienopyrimidinones to Tackle HIV-1 LEDGF/p75-Dependent IN Activity.Molecules (Basel, Switzerland) · 2023Article
- Article
- From Serendipity to Rational Identification of the 5,6,7,8-Tetrahydrobenzo[4,5]thieno[2,3-Pharmaceutics · 2022Article
- Synthesis and characterization of 1,2,4-triazolo[1,5-a]pyrimidine-2-carboxamide-based compounds targeting the PA-PB1 interface of influenza A virus polymerase.European journal of medicinal chemistry · 2021Article
- Scaffold hopping and optimisation of 3',4'-dihydroxyphenyl- containing thienopyrimidinones: synthesis of quinazolinone derivatives as novel allosteric inhibitors of HIV-1 reverse transcriptase-associated ribonuclease H.Journal of enzyme inhibition and medicinal chemistry · 2020Article
- Synthesis of Novel Biocompatible Thienopyrimidine Chromophores with Aggregation-Induced Emission Sensitive to Molecular Aggregation.ACS omega · 2020Article
- 1,2,4-Triazolo[1,5-Molecules (Basel, Switzerland) · 2020Article
- Sensitivity of the C-Terminal Nuclease Domain of Kaposi's Sarcoma-Associated Herpesvirus ORF29 to Two Classes of Active-Site Ligands.Antimicrobial agents and chemotherapy · 2018Article
- Design, Synthesis, and Biological Activity of Tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidine Derivatives as Anti-Inflammatory Agents.Molecules (Basel, Switzerland) · 2017Article
- Design, synthesis and antiviral evaluation of novel heteroarylcarbothioamide derivatives as dual inhibitors of HIV-1 reverse transcriptase-associated RNase H and RDDP functions.Pathogens and disease · 2017Article
- Structural Maturation of HIV-1 Reverse Transcriptase-A Metamorphic Solution to Genomic Instability.Viruses · 2016Review
- Studies on Cycloheptathiophene-3-carboxamide Derivatives as Allosteric HIV-1 Ribonuclease H Inhibitors.ChemMedChem · 2016Article
- Biochemical characterization of a multi-drug resistant HIV-1 subtype AG reverse transcriptase: antagonism of AZT discrimination and excision pathways and sensitivity to RNase H inhibitors.Nucleic acids research · 2016Article
- Article
- Identification of highly conserved residues involved in inhibition of HIV-1 RNase H function by Diketo acid derivatives.Antimicrobial agents and chemotherapy · 2014Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
The thienopyrimidinone 5,6-dimethyl-2-(4-nitrophenyl)thieno[2,3-d]pyrimidin-4(3H)-one (DNTP) occupies the interface between the p66 ribonuclease H (RNase H) domain and p51 thumb of human immunodeficiency virus reverse transcriptase (HIV RT), thereby inducing a conformational change incompatible with catalysis. Here, we combined biochemical characterization of 39 DNTP derivatives with antiviral testing of selected compounds. In addition to wild-type HIV-1 RT, derivatives were evaluated with rationally designed, p66/p51 heterodimers exhibiting high-level DNTP sensitivity or resistance. This strategy identified 3',4'-dihydroxyphenyl (catechol) substituted thienopyrimidinones with submicromolar in vitro activity against both wild type HIV-1 RT and drug-resistant variants. Thermal shift analysis indicates that, in contrast to active site RNase H inhibitors, these thienopyrimidinones destabilize the enzyme, in some instances reducing the Tm by 5 °C. Importantly, catechol-containing thienopyrimidinones also inhibit HIV-1 replication in cells. Our data strengthen the case for allosteric inhibition of HIV RNase H activity, providing a platform for designing improved antagonists for use in combination antiviral therapy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.