Recent contributions of quinolines to antimalarial and anticancer drug discovery research

Walle, Tim Van de; Cools, Lore; Mangelinckx, Sven; D’hooghe, Matthias

doi:10.1016/j.ejmech.2021.113865

Cited by 37 publications

(19 citation statements)

References 291 publications

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“…Quinoline is an abundant pharmacophore in medicinal chemistry and exhibits remarkable pharmacological efficacies such as antituberculosis [ 34 ], antimalarial [ 35 ], antiviral [ 36 , 37 ], anticancer [ 35 , 38 ], antibacterial [ 37 ], antifungal [ 37 , 39 ], antileishmanial [ 40 ], and anti-inflammatory [ 41 ] activity. Moreover, several quinoline-based candidates showed very promising anticancer activities, including neratinib [ 42 ], bosutinib [ 43 ], foretinib [ 44 ], and topotecan [ 45 ], which are currently in clinical trials.…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, several quinoline-based candidates showed very promising anticancer activities, including neratinib [ 42 ], bosutinib [ 43 ], foretinib [ 44 ], and topotecan [ 45 ], which are currently in clinical trials. Additionally, kinase inhibitors [ 35 , 46 , 47 ], apoptotic agents [ 35 , 48 ], microtubule-targeting agents [ 35 , 49 ], topoisomerase inhibitors [ 35 , 50 ], epigenetic enzyme inhibitors [ 35 , 51 ], transcription factor inhibitors [ 35 , 52 ], and carbonic anhydrase inhibitors [ 53 ] are represented ( Figure 2 ).…”

Section: Introductionmentioning

confidence: 99%

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Uracil as a Zn-Binding Bioisostere of the Allergic Benzenesulfonamide in the Design of Quinoline–Uracil Hybrids as Anticancer Carbonic Anhydrase Inhibitors

et al. 2022

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A series of quinoline–uracil hybrids (10a–l) has been rationalized and synthesized. The inhibitory activity against hCA isoforms I, II, IX, and XII was explored. Compounds 10a–l demonstrated powerful inhibitory activity against all tested hCA isoforms. Compound 10h displayed the best selectivity profile with good activity. Compound 10d displayed the best activity profile with minimal selectivity. Compound 10l emerged as the best congener considering both activity (IC50 = 140 and 190 nM for hCA IX and hCA XII, respectively) and selectivity (S.I. = 13.20 and 9.75 for II/IX, and II/XII, respectively). The most active hybrids were assayed for antiproliferative and pro-apoptotic activities against MCF-7 and A549. In silico studies, molecular docking, physicochemical parameters, and ADMET analysis were performed to explain the acquired CA inhibitory action of all hybrids. A study of the structure–activity relationship revealed that bulky substituents at uracil N-1 were unfavored for activity while substituted quinoline and thiouracil were effective for selectivity.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Uracil as a Zn-Binding Bioisostere of the Allergic Benzenesulfonamide in the Design of Quinoline–Uracil Hybrids as Anticancer Carbonic Anhydrase Inhibitors

et al. 2022

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“…The pyridine moiety interacts with nucleophilic and electrophilic substituent while the benzene ring creates the hydrophobic interaction. This specific chemical structure allows interaction with many biological targets, such as topoisomerase, protein kinase, telomerase, tubulin, BCl-2 family protein, protein phosphatase Cdc25, oncogenic Ras, thymidylate synthase, the matrix metalloproteinase, and mitotic kinesin-5 [ 1 , 2 , 3 , 4 , 5 , 6 , 7 ].…”

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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“…Quinoline and its heterocyclic derivatives have been tested by various groups and proved to have many biological activities, including antimalarial, antibacterial, antiviral, and anti-inflammatory activity [ 9 , 10 , 11 ]. Quinoline derivatives have also been extensively studied as potential antitumor agents [ 12 , 13 ]. With the development of cytobiology and molecular biology, the essential principles of tumorigenesis, invasion, migration, and metastasis induced by quinoline derivatives have been further explained.…”

Section: Introductionmentioning

confidence: 99%

The Anticancer Effect of a Novel Quinoline Derivative 91b1 through Downregulation of Lumican

Zhou

Chan

et al. 2022

IJMS

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Quinoline derivatives have been reported to possess a wide range of pharmaceutical activities. Our group previously synthesized a series of quinoline compounds, in which compound 91b1 showed a significant anticancer effect. The purpose of this study was to evaluate the anticancer activity of compound 91b1 in vitro and in vivo, and screen out its regulated target. A series of cancer cell lines and nontumor cell lines were treated with compound 91b1 by MTS cytotoxicity assay and cell-cycle assay. In vivo anticancer activity was evaluated by a xenografted model on nude mice. Target prediction of 91b1 was assessed by microarray assay and confirmed by pancancer analysis. Relative expression of the target gene Lumican was measured by qRT-PCR. 91b1 significantly reduced tumor size in the nude mice xenograft model. Lumican was downregulated after 91b1 treatment. Lumican was proven to increase tumorigenesis in vivo, as well as cancer cell migration, invasion, and proliferation in vitro. The results of this study suggest that the anticancer activity of compound 91b1 probably works through downregulating the gene Lumican.

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Recent contributions of quinolines to antimalarial and anticancer drug discovery research

Cited by 37 publications

References 291 publications

Uracil as a Zn-Binding Bioisostere of the Allergic Benzenesulfonamide in the Design of Quinoline–Uracil Hybrids as Anticancer Carbonic Anhydrase Inhibitors

Uracil as a Zn-Binding Bioisostere of the Allergic Benzenesulfonamide in the Design of Quinoline–Uracil Hybrids as Anticancer Carbonic Anhydrase Inhibitors

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

The Anticancer Effect of a Novel Quinoline Derivative 91b1 through Downregulation of Lumican

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