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Review
. 2022 Jun 24;12(29):18594-18614.
doi: 10.1039/d2ra02896d. eCollection 2022 Jun 22.

Recent advances in chemistry and therapeutic potential of functionalized quinoline motifs - a review

Olayinka O Ajani  1 , King T Iyaye  1 , Olabisi T Ademosun  1
Affiliations
Review

Recent advances in chemistry and therapeutic potential of functionalized quinoline motifs - a review

Olayinka O Ajani et al. RSC Adv. .

Abstract

Quinoline, which consists of benzene fused with N-heterocyclic pyridine, has received considerable attention as a core template in drug design because of its broad spectrum of bioactivity. This review aims to present the recent advances in chemistry, medicinal potential and pharmacological applications of quinoline motifs to unveil their substantial efficacies for future drug development. Essential information in all the current and available literature used was accessed and retrieved using different search engines and databases, including Scopus, ISI Web of Knowledge, Google and PUBMED. Numerous derivatives of the bioactive quinolines have been harnessed via expeditious synthetic approaches, as highlighted herein. This review reveals that quinoline is an indisputable pharmacophore due to its tremendous benefits in medicinal chemistry research and other valuable areas of human endeavour. The recent in vivo and in vitro screening reported by scientists is highlighted herein, which may pave the way for novel drug development. Owing to the array of information available and highlighted herein on the medicinal potential of quinoline and its functionalized derivatives, a new window of opportunity may be opened to medicinal chemists to access more biomolecular quinolines for future drug development.

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Conflict of interest statement

The authors have declared no conflict of interest.

Figures

Fig. 1
Fig. 1. Selected quinoline-based marketed drugs.
Fig. 2
Fig. 2. Chemical structures of quinoline and isoquinoline heterocycles.
Scheme 1
Scheme 1. Synthetic pathway to access unsubstituted quinoline.
Scheme 2
Scheme 2. Friedlander synthetic route for the formation of substituted quinolines.
Scheme 3
Scheme 3. Conrad–Limpach synthetic route for the formation of 4-hydroxyquinoline.
Scheme 4
Scheme 4. Doebner–Miller synthetic route for the formation of substituted quinolines.
Scheme 5
Scheme 5. Synthetic pathway to quinoline derivative 14via Vilsmeier–Haack reaction.
Scheme 6
Scheme 6. Radical-induced rearrangement to afford tetracyclic quinolines.
Scheme 7
Scheme 7. Synthetic pathway to access tricyclic quinolines via Pfitzinger method.
Scheme 8
Scheme 8. One-pot synthetic route to access 2-phenylquinoline-4-carboxylic acid.
Scheme 9
Scheme 9. (a) Povarov synthetic route for the formation of 2-aryl-substituted quinolines. (b) Povarov synthetic route for the formation of tricyclic quinolines.
Scheme 10
Scheme 10. Aza-vinylogous Povarov stereoselective synthesis of substituted quinolines.
Scheme 11
Scheme 11. Hydrogenation reaction of trisubstituted quinoline derivatives.
Scheme 12
Scheme 12. Electrophilic substitution reaction of disubstituted quinoline derivatives.
Scheme 13
Scheme 13. Oxidation reaction of disubstituted quinoline derivatives.
Scheme 14
Scheme 14. Condensation reaction of quinoline derivatives to afford imines.
Fig. 3
Fig. 3. Selected quinoline derivatives with antibacterial activity.
Fig. 4
Fig. 4. Selected quinoline derivatives with anti-malarial activity.
Fig. 5
Fig. 5. Selected quinoline derivatives with c-Met kinase inhibitory activity.
Fig. 6
Fig. 6. Selected quinoline derivatives with anti-leishmanial activity.
Fig. 7
Fig. 7. Selected quinoline derivatives with anti-cancer activity.
Fig. 8
Fig. 8. Selected quinoline derivatives with anti-oxidant activity.
Fig. 9
Fig. 9. Selected quinoline derivatives with anti-inflammatory activity.
Fig. 10
Fig. 10. Selected quinoline derivatives with anti-tubercular activity.
Fig. 11
Fig. 11. Selected quinoline derivatives with antiviral activity.
Fig. 12
Fig. 12. Selected quinoline derivatives with antifungal activity.
Fig. 13
Fig. 13. Selected quinoline derivatives with anti-HIV activity.
Fig. 14
Fig. 14. Selected quinoline derivatives with anti-depressant activity.
Fig. 15
Fig. 15. Selected quinoline derivatives with anti-convulsant activity.
Fig. 16
Fig. 16. Selected quinoline derivatives with anti-diabetic activity.
Fig. 17
Fig. 17. SAR-identified moieties responsible for activity in quinoline-imidazole hybrid 72.
Fig. 18
Fig. 18. SAR-identified moieties responsible for activity in quinine 3.
Fig. 19
Fig. 19. Structures of quinoline-based inhibitors of the growth factor receptor.
Fig. 20
Fig. 20. Cross-talk among EGFR, VEGFR, and c-Met signaling pathways and quinoline-based ligands as their targeted inhibitors.
None
Olayinka O. Ajani
None
King T. Iyaye
None
Olabisi T. Ademosun
See this image and copyright information in PMC

References

    1. Shiro T. Fukaya T. Tobe M. The chemistry and biological activity of heterocycle-fused quinoline derivatives: a review. Eur. J. Med. Chem. 2015;97:397–408. - PubMed
    1. Olateju O. A. Babalola C. P. Olubiyi O. O. Kotila O. A. Kwasi D. A. Oaikhena A. O. Okeke I. N. Quinoline antimalarials increase the antibacterial activity of ampicillin. Front. Microbiol. 2021;12:556550. - PMC - PubMed
    2. Duparc S. Chalon S. Miller S. Richardson N. Toovey S. Neurological and psychiatric safety of tafenoquine in Plasmodium vivax relapse prevention: a review. Malar. J. 2020;19:111. doi: 10.1186/s12936-020-03184-x. - DOI - PMC - PubMed
    3. Das R. R. Jaiswal N. Dev N. Jaiswal N. Naik S. S. Shankar J. Efficacy and safety of anti-malarial drugs (chloroquine and hydroxy-chloroquine) in treatment of covid-19 infection: a systematic review and meta-analysis. Front. Med. 2020;7:482. doi: 10.3389/fmed.2020.00482. - DOI - PMC - PubMed
    4. Sharma V. Mehta D. K. Das R. Synthetic methods of quinoline derivatives as potent anticancer agents. Mini-Rev. Med. Chem. 2017;17(16):1557–1572. - PubMed
    1. Martins P. Jesus J. Santos S. Raposo L. R. Roma-Rodrigues C. Baptista P. V. Fernandes A. R. Heterocyclic anticancer compounds: recent advances and the paradigm shift towards the use of nanomedicine's tool box. Molecules. 2015;20:16852–16891. - PMC - PubMed
    1. Qin S. Q. Li L. C. Song J. R. Li H. Y. Li D. P. Structurally simple phenanthridine analogues based on nitidine and their antitumor activities. Molecules. 2019;24:437. doi: 10.3390/molecules24030437. - DOI - PMC - PubMed
    1. Patil V. Barragan E. Patil S. A. Patil S. A. Bugarin A. Direct synthesis and antimicrobial evaluation of structurally complex chalcones. ChemistrySelect. 2016;1(13):3647–3650.