Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2023 Jan 6:10:1074331.
doi: 10.3389/fchem.2022.1074331. eCollection 2022.

Recent advances in functionalized quinoline scaffolds and hybrids-Exceptional pharmacophore in therapeutic medicine

Oluwadunni F Elebiju  1   2 , Olayinka O Ajani  1   2 , Gbolahan O Oduselu  1   2 , Temitope A Ogunnupebi  1   2 , Ezekiel Adebiyi  1   3   4
Affiliations
Review

Recent advances in functionalized quinoline scaffolds and hybrids-Exceptional pharmacophore in therapeutic medicine

Oluwadunni F Elebiju et al. Front Chem. .

Abstract

Quinoline is one of the most common nitrogen-containing heterocycles owing to its fascinating pharmacological properties and synthetic value in organic and pharmaceutical chemistry. Functionalization of this moiety at different positions has allowed for varying pharmacological activities of its derivative. Several publications over the last few decades have specified various methods of synthesis. This includes classical methods of synthesizing the primary quinoline derivatives and efficient methods that reduce reaction time with increased yield employing procedures that fulfill one of the twelve green chemistry principles, "safer solvent". The metal nanoparticle-catalyzed reaction also serves as a potent and effective technique for the synthesis of quinoline with excellent atom efficiency. The primary focus of this review is to highlight the routes to synthesizing functionalized quinoline derivatives, including hybrids that have moieties with predetermined activities bound to the quinoline moiety which are of interest in synthesizing drug candidates with dual modes of action, overcoming toxicity, and resistance amongst others. This was achieved using updated literature, stating the biological activities and mechanisms through which these compounds administer relief. The ADMET studies and Structure-Activity Relationship (SAR) of novel derivatives were also highlighted to explore the drug-likeness of the quinoline-hybrids and the influence of substituent characteristics and position on the biological activity of the compounds.

Keywords: admet; drug design; hybrid; pharmacological activity; quinoline; synthesis.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Chemical and 3D structure of quinoline.
FIGURE 2
FIGURE 2
Structures of some commercially available quinoline containing drugs.
FIGURE 3
FIGURE 3
Structures of reported quinoline hybrids.
FIGURE 4
FIGURE 4
Classical synthetic route of quinoline.
SCHEME 1
SCHEME 1
Conrad-Limpach cyclo condensation for the synthesis of ibuprofen-quinoline hybrid.
SCHEME 2
SCHEME 2
Vilsmeier-Haack synthesis of pyrazole and pyridine-quinoline hybrids.
SCHEME 3
SCHEME 3
Vilsmeier-Haack synthesis of quinoline-triazole hybrids.
SCHEME 4
SCHEME 4
Vilsmeier-Haack synthesis of quinoline-carbaldehyde derivatives.
SCHEME 5
SCHEME 5
Microwave-assisted synthesis of fused quinoline-thiones.
SCHEME 6
SCHEME 6
Microwave-assisted condensation of hydrazide-hydrazone quinoline derivatives.
SCHEME 7
SCHEME 7
Ultrasound-assisted quinoline imidazolium salts synthesis.
SCHEME 8
SCHEME 8
Ultrasound-assisted synthesis of 2-substituted quinolones.
SCHEME 9
SCHEME 9
CuNPs mediated Knoevenagel condensation.
SCHEME 10
SCHEME 10
Synthesis of quinoline hybrid via click chemistry.
FIGURE 5
FIGURE 5
Hydrazide-hydrazone-quinoline hybrids with antimicrobial activity.
FIGURE 6
FIGURE 6
Quinoline-oxadiazole hybrid with antitubercular Activities.
FIGURE 7
FIGURE 7
Quinolone derivatives with antiproliferative activity.
FIGURE 8
FIGURE 8
Quinoline hybrids with antileishmanial activity.
FIGURE 9
FIGURE 9
Quinoline hybrids with a-glucosidase inhibitory activity.
SCHEME 11
SCHEME 11
Mechanism of compound 51 scavenging activity.
FIGURE 10
FIGURE 10
Derivatives with anti-inflammatory activity.
FIGURE 11
FIGURE 11
Ibuprofen-quinoline hybrids with anti-inflammatory activity.
FIGURE 12
FIGURE 12
quinoline derivatives with antimalaria activity.
FIGURE 13
FIGURE 13
Some quinoline derivatives with reported SAR.
FIGURE 14
FIGURE 14
SAR studies showing change in potency of quinoline derivatives as substituent changes.
FIGURE 15
FIGURE 15
SAR activity of Ibuprofen-quinolinyl hybrids.
FIGURE 16
FIGURE 16
Quinoline-Indole-Schiff base derivative.
FIGURE 17
FIGURE 17
Quinoline-fluoroproline amide and quinoline-imine hybrids with reported insilico ADMET.
See this image and copyright information in PMC

References

    1. Abdelbaset M. S., Abdel-Aziz M., Abuo-Rahma G. E. D. A., Abdelrahman M. H., Ramadan M., Youssif B. G. M. (2018). Novel quinoline derivatives carrying nitrones/oximes nitric oxide donors: Design, synthesis, antiproliferative and caspase-3 activation activities. Arch. Pharm. 352 (1), 1800270. 10.1002/ardp.201800270 - DOI - PubMed
    1. Ajani O. O., Iyaye K. T., Audu O. Y., Olorunshola S. J., Kuye A. O., Olanrewaju I. O. (2018). Microwave assisted synthesis and antimicrobial potential of quinoline-based 4-hydrazide-hydrazone derivatives. J. Heterocycl. Chem. 55 (1), 302–312. 10.1002/jhet.3050 - DOI
    1. Almandil N. B., Taha M., Rahim F., Wadood A., Imran S., Alqahtani M. A., et al. (2019). Synthesis of novel quinoline-based thiadiazole, evaluation of their antileishmanial potential and molecular docking studies. Bioorg. Chem. 85, 109–116. 10.1016/j.bioorg.2018.12.025 - DOI - PubMed
    1. Angajala G., Aruna V., Subashini R. (2020). An efficient nano-copper catalyzed base-free Knoevenagel condensation: A facile synthesis, molecular modelling simulations, SAR and hypoglycemic studies of new quinoline tethered acridine analogues as PPARγ agonists. J. Mol. Struct. 1220, 128601. 10.1016/j.molstruc.2020.128601 - DOI
    1. Costa C. A., Lopes R. M., Ferraz L. S., Esteves G. N., Di Iorio J. F., Souza A. A., et al. (2020). Cytotoxicity of 4-substituted quinoline derivatives: Anticancer and antileishmanial potential. Bioorg. Med. Chem. 28 (11), 115511. 10.1016/j.bmc.2020.115511 - DOI - PubMed