ArticleJournal of medicinal chemistry2015
N-Substituted Quinolinonyl Diketo Acid Derivatives as HIV Integrase Strand Transfer Inhibitors and Their Activity against RNase H Function of Reverse Transcriptase.
Article in Journal of medicinal chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- Targeting Human Immunodeficiency Virus Integrase Beyond the Active Site: The Discovery and Development of Allosteric Integrase Inhibitors.ChemMedChem · 2026Review
- Quinolinonyl Derivatives as Dual Inhibitors of the HIV-1 Integrase Catalytic Site and Integrase-RNA interactions.ACS medicinal chemistry letters · 2024Article
- Enhanced Selectivity in 4-Quinolone Formation: A Dual-Base System for Palladium-Catalyzed Carbonylative Cyclization with Fe(CO)Molecules (Basel, Switzerland) · 2024Article
- Strategies in the Design and Development of Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs).Viruses · 2023Review
- Flavonoids and Acid-Hydrolysis derivatives ofJournal of enzyme inhibition and medicinal chemistry · 2021Article
- Quinolinonyl Non-Diketo Acid Derivatives as Inhibitors of HIV-1 Ribonuclease H and Polymerase Functions of Reverse Transcriptase.Journal of medicinal chemistry · 2021Article
- Investigation ofPharmaceuticals (Basel, Switzerland) · 2021Article
- HIV-1 Reverse Transcriptase/Integrase Dual Inhibitors: A Review of Recent Advances and Structure-activity Relationship Studies.Iranian journal of pharmaceutical research : IJPR · 2021Review
- Classification and Design of HIV-1 Integrase Inhibitors Based on Machine Learning.Computational and mathematical methods in medicine · 2021Article
- Pyrrolyl Pyrazoles as Non-Diketo Acid Inhibitors of the HIV-1 Ribonuclease H Function of Reverse Transcriptase.ACS medicinal chemistry letters · 2020Article
- Recent advances in the discovery of small-molecule inhibitors of HIV-1 integrase.Future science OA · 2018Review
- Structure-Driven Discovery of α,γ-Diketoacid Inhibitors Against UL89 Herpesvirus Terminase.ACS omega · 2018Article
- The Current Case of Quinolones: Synthetic Approaches and Antibacterial Activity.Molecules (Basel, Switzerland) · 2016Review
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Authors and funding
20 authors.
Funding
Abstract
Bifunctional quinolinonyl DKA derivatives were first described as nonselective inhibitors of 3'-processing (3'-P) and strand transfer (ST) functions of HIV-1 integrase (IN), while 7-aminosubstituted quinolinonyl derivatives were proven IN strand transfer inhibitors (INSTIs) that also displayed activity against ribonuclease H (RNase H). In this study, we describe the design, synthesis, and biological evaluation of new quinolinonyl diketo acid (DKA) derivatives characterized by variously substituted alkylating groups on the nitrogen atom of the quinolinone ring. Removal of the second DKA branch of bifunctional DKAs, and the amino group in position 7 of quinolinone ring combined with a fine-tuning of the substituents on the benzyl group in position 1 of the quinolinone, increased selectivity for IN ST activity. In vitro, the most potent compound was 11j (IC50 = 10 nM), while the most active compounds against HIV infected cells were ester derivatives 10j and 10l. In general, the activity against RNase H was negligible, with only a few compounds active at concentrations higher than 10 μM. The binding mode of the most potent IN inhibitor 11j within the IN catalytic core domain (CCD) is described as well as its binding mode within the RNase H catalytic site to rationalize its selectivity.
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