5,8-Quinolinedione Scaffold as a Promising Moiety of Bioactive Agents

Kadela-Tomanek, Monika; Bębenek, Ewa; Chrobak, Elwira; Boryczka, Stanisław

doi:10.3390/molecules24224115

Cited by 26 publications

(15 citation statements)

References 100 publications

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“…The Streptomyces species produce compounds containing the 5,8-quinolinedione moiety, such as streptonigrin , lavendamycin , and streptonigron , which exhibit a wide spectrum of biological activity ( Figure 1 ) [ 8 , 9 ]. Previous studies dealt with the modification of 5,8-quinolinedione moiety at the C-2, C-6, and C-7 positions and they showed that such modification can lead to changes in biological activity [ 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 ].…”

Section: Introductionmentioning

confidence: 99%

“…The tested compounds contain two active moieties, i.e., 1,4-quinone and betulin. The main mechanism of activity for 1,4-quinone derivatives is the interaction with NQO1 protein, for which the overexpression is observed in many types of cancer cell lines [ 8 , 10 , 24 ]. The betulin derivatives show a wide spectrum of activities including anticancer, antiviral, antibacterial, and anti-inflammatory effects.…”

Section: Introductionmentioning

confidence: 99%

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Lipophilicity, Pharmacokinetic Properties, and Molecular Docking Study on SARS-CoV-2 Target for Betulin Triazole Derivatives with Attached 1,4-Quinone

et al. 2021

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A key parameter in the design of new active compounds is lipophilicity, which influences the solubility and permeability through membranes. Lipophilicity affects the pharmacodynamic and toxicological profiles of compounds. These parameters can be determined experimentally or by using different calculation methods. The aim of the research was to determine the lipophilicity of betulin triazole derivatives with attached 1,4-quinone using thin layer chromatography in a reverse phase system and a computer program to calculate its theoretical model. The physiochemical and pharmacokinetic properties were also determined by computer programs. For all obtained parameters, the similarity analysis and multilinear regression were determined. The analyses showed that there is a relationship between structure and properties under study. The molecular docking study showed that betulin triazole derivatives with attached 1,4-quinone could inhibit selected SARS-CoV-2 proteins. The MLR regression showed that there is a correlation between affinity scoring values (ΔG) and the physicochemical properties of the tested compounds.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Lipophilicity, Pharmacokinetic Properties, and Molecular Docking Study on SARS-CoV-2 Target for Betulin Triazole Derivatives with Attached 1,4-Quinone

et al. 2021

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“…However, due to their toxicity, only a few compounds were evaluated in clinical trials. Attempts to design and synthesize analogues endowed with lower toxicity are currently being performed [ 25 ].…”

Section: Naphthoquinone and Quinolinedione Scaffolds In Antitumor Hyb...mentioning

confidence: 99%

“…The alkaloid streptonigrin isolated from Streptomyces displaying anti-leukemic properties, and the ascidian metabolites ascidiathiazones A and B are examples of molecules belonging to this class. This moiety is considered promising in the synthesis of bioactive agents [ 25 ]. However, to date few studies have been reported considering this scaffold in the synthesis of anticancer hybrids.…”

Section: Design Synthesis and Biological Evaluation Of Antitumor Hybridsmentioning

confidence: 99%

Hybrid Molecules Containing Naphthoquinone and Quinolinedione Scaffolds as Antineoplastic Agents

et al. 2022

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In recent decades, molecular hybridization has proven to be an efficient tool for obtaining new synthetic molecules to treat different diseases. Based on the core idea of covalently combining at least two pharmacophore fragments present in different drugs and/or bioactive molecules, the new hybrids have shown advantages when compared with the compounds of origin. Hybridization could be successfully applied to anticancer drug discovery, where efforts are underway to develop novel therapeutics which are safer and more effective than those currently in use. Molecules presenting naphthoquinone moieties are involved in redox processes and in other molecular mechanisms affecting cancer cells. Naphthoquinones have been shown to inhibit cancer cell growth and are considered privileged structures and useful templates in the design of hybrids. The present work aims at summarizing the current knowledge on antitumor hybrids built using 1,4- and 1,2-naphthoquinone (present in natural compounds as lawsone, napabucasin, plumbagin, lapachol, α-lapachone, and β -lapachone), and the related quinolone- and isoquinolinedione scaffolds reported in the literature up to 2021. In detail, the design and synthetic approaches adopted to produce the reported compounds are highlighted, the structural fragments considered in hybridization and their biological activities are described, and the structure–activity relationships and the computational analyses applied are underlined.

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“…For example, natural, such as streptonigrin, and synthetic 5,8-quinolinedione compounds show wide spectrum of biological activities such as anticancer, antibacterial, and antiviral. The activity depends on the substituent at the positions C-6, C-7 and C-2 of the 5,8-quinolinedione moiety ( Figure 1 ) [ 12 , 13 , 14 , 15 , 16 ].…”

Section: Introductionmentioning

confidence: 99%

Hybrids of 1,4-Quinone with Quinoline Derivatives: Synthesis, Biological Activity, and Molecular Docking with DT-Diaphorase (NQO1)

et al. 2022

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Hybrids 1,4-quinone with quinoline were obtained by connecting two active structures through an oxygen atom. This strategy allows to obtain new compounds with a high biological activity and suitable bioavailability. Newly synthesized compounds were characterized by various spectroscopic methods. The enzymatic assay used showed that these compounds were a suitable DT-diaphorase (NQO1) substrates as evidenced by increasing enzymatic conversion rates relative to that of streptonigrin. Hybrids were tested in vitro against a panel of human cell lines including melanoma, breast, and lung cancers. They showed also a high cytotoxic activity depending on the type of 1,4-quinone moiety and the applied tumor cell lines. It was found that cytotoxic activity of the studied hybrids was increasing against the cell lines with higher NQO1 protein level, such as breast (MCF-7 and T47D) and lung (A549) cancers. Selected hybrids were tested for the transcriptional activity of the gene encoding a proliferation marker (H3 histone), cell cycle regulators (p53 and p21) and the apoptosis pathway (BCL-2 and BAX). The molecular docking was used to examine the probable interaction between the hybrids and NQO1 protein.

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5,8-Quinolinedione Scaffold as a Promising Moiety of Bioactive Agents

Cited by 26 publications

References 100 publications

Lipophilicity, Pharmacokinetic Properties, and Molecular Docking Study on SARS-CoV-2 Target for Betulin Triazole Derivatives with Attached 1,4-Quinone

Lipophilicity, Pharmacokinetic Properties, and Molecular Docking Study on SARS-CoV-2 Target for Betulin Triazole Derivatives with Attached 1,4-Quinone

Hybrid Molecules Containing Naphthoquinone and Quinolinedione Scaffolds as Antineoplastic Agents

Hybrids of 1,4-Quinone with Quinoline Derivatives: Synthesis, Biological Activity, and Molecular Docking with DT-Diaphorase (NQO1)

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