ArticleJournal of medicinal chemistry2016
Design, Synthesis, and Biological Evaluations of Hydroxypyridonecarboxylic Acids as Inhibitors of HIV Reverse Transcriptase Associated RNase H.
Article in Journal of medicinal chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 63 citations in OpenAlex.
- Computational design, synthesis and biological evaluation of novel pyridinone derivatives as NNRTIs.Scientific reports · 2026Article
- Asymmetric Total Synthesis of (-)-Verrucarol.Angewandte Chemie (International ed. in English) · 2026Article
- Design, Synthesis and Biological Evaluation of 3-Hydrazonoindolin-2-one Derivatives as Novel HIV-1 RNase H Inhibitors.Molecules (Basel, Switzerland) · 2025Article
- Fragment-Based Discovery of Novel MUS81 Inhibitors.ACS medicinal chemistry letters · 2024Article
- Structure-Based Design of Novel Thiazolone[3,2-Molecules (Basel, Switzerland) · 2024Article
- Molecular Modeling of Brassicaceae Derivatives for Inhibiting Lipoxygenases: A Promising Therapeutic Strategy.Current drug discovery technologies · 2024Article
- Inhibiting HCMV pUL89-C Endonuclease with Metal-Binding Compounds.Journal of medicinal chemistry · 2023Review
- Targeting Ribonucleases with Small Molecules and Bifunctional Molecules.ACS chemical biology · 2023Review
- Targeting Metalloenzymes: The "Achilles' Heel" of Viruses and Parasites.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Discovery ofActa pharmaceutica Sinica. B · 2022Article
- Pivotal role of a conserved histidine in Escherichia coli ribonuclease HI as proposed by X-ray crystallography.Acta crystallographica. Section D, Structural biology · 2022Article
- Metal binding 6-arylthio-3-hydroxypyrimidine-2,4-diones inhibited human cytomegalovirus by targeting the pUL89 endonuclease of the terminase complex.European journal of medicinal chemistry · 2021Article
- Avoiding Drug Resistance in HIV Reverse Transcriptase.Chemical reviews · 2021Review
- Small Molecules-Prospective Novel HCMV Inhibitors.Viruses · 2021Review
- Retroviral RNase H: Structure, mechanism, and inhibition.The Enzymes · 2021Review
- Cutting into the Substrate Dominance: Pharmacophore and Structure-Based Approaches toward Inhibiting Human Immunodeficiency Virus Reverse Transcriptase-Associated Ribonuclease H.Accounts of chemical research · 2020Review
- Determinants of Active-Site Inhibitor Interaction with HIV-1 RNase H.ACS infectious diseases · 2019Article
- Design, synthesis, and biologic evaluation of novel galloyl derivatives as HIV-1 RNase H inhibitors.Chemical biology & drug design · 2019Article
- Pharmacophore-based design of novel 3-hydroxypyrimidine-2,4-dione subtypes as inhibitors of HIV reverse transcriptase-associated RNase H: Tolerance of a nonflexible linker.European journal of medicinal chemistry · 2019Article
- Targeting Metalloenzymes for Therapeutic Intervention.Chemical reviews · 2019Review
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Targeting the clinically unvalidated reverse transcriptase (RT) associated ribonuclease H (RNase H) for human immunodeficiency virus (HIV) drug discovery generally entails chemotypes capable of chelating two divalent metal ions in the RNase H active site. The hydroxypyridonecarboxylic acid scaffold has been implicated in inhibiting homologous HIV integrase (IN) and influenza endonuclease via metal chelation. We report herein the design, synthesis, and biological evaluations of a novel variant of the hydroxypyridonecarboxylic acid scaffold featuring a crucial N-1 benzyl or biarylmethyl moiety. Biochemical studies show that most analogues consistently inhibited HIV RT-associated RNase H in the low micromolar range in the absence of significant inhibition of RT polymerase or IN. One compound showed reasonable cell-based antiviral activity (EC50 = 10 μM). Docking and crystallographic studies corroborate favorable binding to the active site of HIV RNase H, providing a basis for the design of more potent analogues.
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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.