ArticleProceedings of the National Academy of Sciences of the United States of America2012
Probing chelation motifs in HIV integrase inhibitors.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
23 citing papers in PubMed, 49 citations in OpenAlex.
- Bidentate Metal-Binding Motifs in US FDA Approved Small Molecule Drugs.Journal of medicinal chemistry · 2026Review
- Ligand-to-Ligand Charge Transfer (LL'CT) Transitions in Square-Planar Metal-Bipyridyl Complexes of Heteroatom-Substituted Maltol Derivatives.Inorganic chemistry · 2026Article
- Quinolinonyl Derivatives as Dual Inhibitors of the HIV-1 Integrase Catalytic Site and Integrase-RNA interactions.ACS medicinal chemistry letters · 2024Article
- Carboxylic Acid Isostere Derivatives of Hydroxypyridinones as Core Scaffolds for Influenza Endonuclease Inhibitors.ACS medicinal chemistry letters · 2023Article
- Evaluation of a flavonoid library for inhibition of interaction of HIV-1 integrase with human LEDGF/p75 towards a structure-activity relationship.Annals of medicine · 2022Article
- Novel 2-(Diphenylmethylidene) Malonic Acid Derivatives as Anti-HIV Agents: Molecular Modeling, Synthesis and Biological Evaluation.Iranian journal of pharmaceutical research : IJPR · 2022Article
- Antibacterial activity of 2-amino-4-hydroxypyrimidine-5-carboxylates and binding to Burkholderia pseudomallei 2-C-methyl-d-erythritol-2,4-cyclodiphosphate synthase.Bioorganic & medicinal chemistry letters · 2019Article
- Structural and Functional Studies of Bacterial Enolase, a Potential Target against Gram-Negative Pathogens.Biochemistry · 2019Article
- Targeting Metalloenzymes for Therapeutic Intervention.Chemical reviews · 2019Review
- Structure-Activity Relationships in Metal-Binding Pharmacophores for Influenza Endonuclease.Journal of medicinal chemistry · 2018Article
- Rapid activity prediction of HIV-1 integrase inhibitors: harnessing docking energetic components for empirical scoring by chemometric and artificial neural network approaches.Journal of computer-aided molecular design · 2016Article
- Progress in HIV-1 Integrase Inhibitors: A Review of their Chemical Structure Diversity.Iranian journal of pharmaceutical research : IJPR · 2016Review
- N-Substituted Quinolinonyl Diketo Acid Derivatives as HIV Integrase Strand Transfer Inhibitors and Their Activity against RNase H Function of Reverse Transcriptase.Journal of medicinal chemistry · 2015Article
- The hepatitis B virus ribonuclease H as a drug target.Antiviral research · 2015Review
- An integrated biological approach to guide the development of metal-chelating inhibitors of influenza virus PA endonuclease.Molecular pharmacology · 2015Article
- Inhibitors of nucleotidyltransferase superfamily enzymes suppress herpes simplex virus replication.Antimicrobial agents and chemotherapy · 2014Article
- Exploring the influence of the protein environment on metal-binding pharmacophores.Journal of medicinal chemistry · 2014Article
- New β-lactamase inhibitors: a therapeutic renaissance in an MDR world.Antimicrobial agents and chemotherapy · 2014Review
- Investigating the selectivity of metalloenzyme inhibitors.Journal of medicinal chemistry · 2013Article
- Clawing back: broadening the notion of metal chelators in medicine.Current opinion in chemical biology · 2013Review
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
A series of HIV integrase (HIV-1 IN) inhibitors were synthesized to evaluate the role of the metal-binding group (MBG) in this class of metalloenzyme inhibitors. A total of 21 different raltegravir-chelator derivative (RCD) compounds were prepared that differed only in the nature of the MBG. These IN strand-transfer inhibitors (INSTIs) were evaluated in vitro in cell-free enzyme activity assays, and the in vitro results were further validated in cell culture experiments. All of the active compounds showed selective inhibition of the strand-transfer reaction over 3'-processing, suggesting a common mode of action with raltegravir. The results of the in vitro activity suggest that the nature of the MBG donor atoms, the overall MBG structure, and the specific arrangement of the MBG donor atom triad are essential for obtaining maximal HIV-1 IN inhibition. At least two compounds (RCD-4, RCD-5) containing a hydroxypyrone MBG were found to display superior strand-transfer inhibition when compared to an abbreviated analogue of raltegravir (RCD-1). By isolating and examining the role of the MBG in a series of INSTIs, we have identified a scaffold (hydroxypyrones) that may provide access to a unique class of HIV-1 IN inhibitors, and may help overcome rising raltegravir resistance.
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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.