Tailored Quinolines Demonstrate Flexibility to Exert Antitumor Effects through Varied Mechanisms-A Medicinal Perspective

Abstract

Background: Quinoline is considered to be a privileged heterocyclic ring owing to its presence in diverse scaffolds endowed with promising activity profiles. In particular, quinoline containing compounds have exhibited substantial antiproliferative effects through the diverse mechanism of actions, which indicates that the heteroaryl unit is flexible as well as accessible to subtle structural changes that enable its inclusion in chemically distinct anti-tumor constructs.

Methods: Herein, we describe a medicinal chemistry perspective on quinolines as anticancer agents by digging into the peer-reviewed literature as well as patents published in the past few years.

Results: This review will serve as a guiding tool for medicinal chemists and chemical biologists to gain insights about the benefits of quinoline ring installation to tune the chemical architectures for inducing potent anticancer effects.

Conclusion: Quinoline ring containing anticancer agents presents enough optimism and promise in the field of drug discovery to motivate the researchers towards the continued explorations on such scaffolds. It is highly likely that adequate efforts in this direction might yield some potential cancer therapeutics in the future.

Keywords: Quinoline; anticancer; cell line; cytotoxic; heterocycle; medicinal; scaffold.

Fig. 1

Quinoline containing anticancer drugs

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HDAC inhibitors

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Topoisomerase inhibitors

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Tubulin inhibitors

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Tubulin inhibitors

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Kinase inhibitors

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Kinase inhibitors

Fig. 7

Kinase inhibitors

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Anticancer quinolines

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Anticancer quinolines

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Anticancer quinolines

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Anticancer quinolines

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Quinoline derivatives as PI3K alpha enzyme inhibitors

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Imidazo[4,5-c]quinoline derivatives with cancer cell lines for which IC₅₀ value is less than 1μM

Fig. 14

Quinoline compounds as hMetAP enzyme inhibitors with IC₅₀ values (in μM)

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Anticancer quinolines

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4-Anilinofuro[2,3-b]quinoline derivatives

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Quinoline derivatives as c-Met kinase inhibitors

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Imidazo[4,5-c]quinoline compounds as DNA-protein kinase inhibitors

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2-Selenophene-4-quinolones derivatives with IC₅₀ (μM) values

Fig. 20

Substituted quinoline compounds as c-Met kinase inhibitors

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Anticancer quinolines

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Anticancer quinolines

Fig. 23

Anticancer quinolines

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Quinoline derivatives with relative MTS activity at 50 μg/ml concentration

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Quinoline derivatives as AXL inhibitor

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Heterocyclic quinoline compounds as Glycogen Synthase kinase-3 (GSK-3) inhibitors

Fig. 27

Substituted quinoline compounds with IC₅₀ values in nM range

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4-Aminoquinoline derivatives as APE-1 enzyme inhibitors

Fig. 29

Substituted 2,3-dihydroimidazo[1,2-c]quinoline derivatives as PI3 kinase enzyme inhibitors

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Trisubstituted bicyclic quinoline derivatives as kinase inhibitors

Fig. 31

Anticancer quinolines

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Quinoline sulfonyl derivatives

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Imidazo[4,5-c]quinoline derivatives as LRRK2 inhibitors

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Quinoline derivatives as anticancer compounds

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Fused quinoline compounds as mTOR inhibitory activity

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Arylquinazoline compounds as DNA-protein kinase inhibitors

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Novel quinoline derivatives

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Quinoline derivatives as Axl inhibitor

Fig. 39

Bisaminoquinoline derivatives