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
. 2022 Jul 1;23(7):2507-2521.
doi: 10.31557/APJCP.2022.23.7.2507.

Newly Substituted Anilino-Fluoroquinolones with Proliferation Inhibition Potential against a Panel of Cancer Cell Lines

Mohammed Ameen Fouad Salih  1 , Yusuf Al-Hiari  1   2 , Violet Kasabri  1 , Rula Darwish  1 , Hamza Abumansour  2 , Laurance Bourghli  2 , Sundus Al Alawi  1 , Rabab Albashiti  1
Affiliations

Newly Substituted Anilino-Fluoroquinolones with Proliferation Inhibition Potential against a Panel of Cancer Cell Lines

Mohammed Ameen Fouad Salih et al. Asian Pac J Cancer Prev. .

Abstract

Background: From a chemistry point of view, we hypothesized that superlative dual cytotoxicity-radical scavenging bioefficacies of series 4 FQs correlate to their acidic groups and C8-C7 ethylene diamine Chelation Bridge.

Methodology: Newly synthesized 16 lipophilic-acid chelating FQs have been screened for in vitro duality of proliferation inhibition and radical scavenging capacities.

Results: Substantially in LPS prompted RAW264.7 macrophages inflammation, IC50 values (µM) in the ascending order of new FQs' NO scavenging/antiinflammation capacity were 4e<4b<3d<4f<5c0.05). In comparison to classical and robust antineoplastic agent cisplatin and unlike triazoloFQs; nitroFQs (3a, 3b and 3f) and the reduced FQs (4a, 4c, 4d and 4e) exerted antiproliferation IC50 values <50 µM in leukaemia K562. Besides nitroFQ 3, the reduced FQs (4c and 4f) exhibited antineoplastic IC50 values <50 µM in lung A549 carcinoma. NitroFQ 3c and reduced FQs 4b, 4c, and 4f in breast MCF7 and reduced 4c in pancreatic PANC1 had reduction of viability IC50 values <50 µM. NitroFQ 3e, reduced FQs 4b and, 4c and triazoloFQ 5a exerted antiproliferation IC50 values <50 µM in breast T47D cells. Also nitroFQ 3e, reduced FQ 4c and triazoloFQ 5f exhibited antineoplastic IC50 values <50 µM in PC3 prostate cancer cells. Exceptionally triazoloFQ 5a, but neither nitro- nor reduced FQs, had cytotoxicity IC50 value <50 µM in resistant melanoma A375 cells. Unequivocally 4b antineoplastic effectiveness linked with its radical scavenging and antiinflammation effects while 3d and 5c lacked matching antiproliferation potentialities to their exquisite antiinflammation capacities. Explicitly reduced 4e and 4f exerted antiinflammation-selective cytotoxicity duality in vitro.

Conclusion: Collectively, this work reveals lipophilic-acidic chelator FQs as authentic agents for the repurposing approach in anticancer chemotherapy/prevention.

Keywords: Antiinflammation and antiCancer; Cisplatin; Fluoroquinolones and Triazoloquinolones; NO-radical scavenging; Sulphorodhamine B and Greiss assay.

PubMed Disclaimer

Conflict of interest statement

Authors declare no conflict of interest

Figures

Chart 1
Chart 1
Target FQs with more Lipophilic
Figure 1
Figure 1
Order of Activity Based on the Structural Scaffold in a Strong Group against K562
Chart 2
Chart 2
Representative FQs Drugs
Figure 2
Figure 2
4''-methoxy Substitution Effect on Activity K562
Figure 3
Figure 3
Possible Effects that Explain the Weak Activity of 4a
Figure 4
Figure 4
Effect of Methoxy Substitution in 4c and 4a against All Cell Lines Tested
Figure 5
Figure 5
C-8 Amino Group in 4c
Figure 6a
Figure 6a
Contribution of C-8 Amino Group (4 series) in Anti-Proliferative Activity; A- H-B; B-Chelating agents, C-Antioxidant and D- 1,8-bridging (rigidity)
Figure 6b
Figure 6b
Chelator Groups Shared by All Anti Proliferating FQs and Doxorubicin
See this image and copyright information in PMC

References

    1. AbdulFattah T, Saeed A, Al-Hiari YM, et al. Functionalized Furo[3,2-c] coumarins as Anti-proliferative, Anti-lipolytic, and Antiinflammatory Compounds: Synthesis and Molecular Docking Studies. J Mol Struc. 2019;1179:390–400.
    1. Alabsi Y, Al-Hiari Y, Kasabri V, et al. In vitro modulation of pancreatic lipase and proliferation of obesity related-colorectal cancer cell line panel by novel synthetic FQs. Rev Roum Chim. 2018;63:1123–34.
    1. AlHallaq T, Al-Hiari Y, Kasabri V, et al. In vitro Antiproliferative Properties of Lipophililic -Acid Chelating Fluoroquinolones and triazoloFluoroquinolones with 7-dihaloanilinosubstitution. AntiCancer Agents Med Chem. 2022 Accepted. - PubMed
    1. AlKhalil M, Al-Hiari Y, Kasabri V, et al. Selected pharmacotherapy agents as antiproliferative and antiinflammatory compounds. Drug Dev Res. 2020;81:470–90. - PubMed
    1. Al-Nuaimi A, Al-Hiari Y, Haddadin R, et al. A Novel class of Functionalized Synthetic Fluoroquinolones with Dual Antiproliferative - Antimicrobial Capacities. Asian Pac J Cancer Prev. 2021;22:1075–86. - PMC - PubMed