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A Nitronaphthalimide Probe for Fluorescence Imaging of Hypoxia in Cancer Cells
The bioreductive enzymes typically upregulated in hypoxic tumor cells can be targeted for developing diagnostic and drug delivery applications. In this study, a new fluorescent probe 4−(6−nitro−1,3−dioxo−1H−benzo[de]isoquinolin−2(3H)−yl)benzaldehyde (NIB) based on a nitronaphthalimide skeleton that...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer US
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8545720/ https://www.ncbi.nlm.nih.gov/pubmed/34383168 http://dx.doi.org/10.1007/s10895-021-02800-6 |
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author | Kumari, Rashmi R, Vasumathy Sunil, Dhanya Ningthoujam, Raghumani Singh Pandey, Badri Narain Kulkarni, Suresh D. Varadavenkatesan, Thivaharan Venkatachalam, Ganesh V, Anil Kumar N. |
author_facet | Kumari, Rashmi R, Vasumathy Sunil, Dhanya Ningthoujam, Raghumani Singh Pandey, Badri Narain Kulkarni, Suresh D. Varadavenkatesan, Thivaharan Venkatachalam, Ganesh V, Anil Kumar N. |
author_sort | Kumari, Rashmi |
collection | PubMed |
description | The bioreductive enzymes typically upregulated in hypoxic tumor cells can be targeted for developing diagnostic and drug delivery applications. In this study, a new fluorescent probe 4−(6−nitro−1,3−dioxo−1H−benzo[de]isoquinolin−2(3H)−yl)benzaldehyde (NIB) based on a nitronaphthalimide skeleton that could respond to nitroreductase (NTR) overexpressed in hypoxic tumors is designed and its application in imaging tumor hypoxia is demonstrated. The docking studies revealed favourable interactions of NIB with the binding pocket of NTR-Escherichia coli. NIB, which is synthesized through a simple and single step imidation of 4−nitro−1,8−naphthalic anhydride displayed excellent reducible capacity under hypoxic conditions as evidenced from cyclic voltammetry investigations. The fluorescence measurements confirmed the formation of identical products (NIB-red) during chemical as well as NTR−aided enzymatic reduction in the presence of NADH. The potential fluorescence imaging of hypoxia based on NTR-mediated reduction of NIB is confirmed using in-vitro cell culture experiments using human breast cancer (MCF−7) cells, which displayed a significant change in the fluorescence colour and intensity at low NIB concentration within a short incubation period in hypoxic conditions. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10895-021-02800-6. |
format | Online Article Text |
id | pubmed-8545720 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Springer US |
record_format | MEDLINE/PubMed |
spelling | pubmed-85457202021-10-29 A Nitronaphthalimide Probe for Fluorescence Imaging of Hypoxia in Cancer Cells Kumari, Rashmi R, Vasumathy Sunil, Dhanya Ningthoujam, Raghumani Singh Pandey, Badri Narain Kulkarni, Suresh D. Varadavenkatesan, Thivaharan Venkatachalam, Ganesh V, Anil Kumar N. J Fluoresc Original Article The bioreductive enzymes typically upregulated in hypoxic tumor cells can be targeted for developing diagnostic and drug delivery applications. In this study, a new fluorescent probe 4−(6−nitro−1,3−dioxo−1H−benzo[de]isoquinolin−2(3H)−yl)benzaldehyde (NIB) based on a nitronaphthalimide skeleton that could respond to nitroreductase (NTR) overexpressed in hypoxic tumors is designed and its application in imaging tumor hypoxia is demonstrated. The docking studies revealed favourable interactions of NIB with the binding pocket of NTR-Escherichia coli. NIB, which is synthesized through a simple and single step imidation of 4−nitro−1,8−naphthalic anhydride displayed excellent reducible capacity under hypoxic conditions as evidenced from cyclic voltammetry investigations. The fluorescence measurements confirmed the formation of identical products (NIB-red) during chemical as well as NTR−aided enzymatic reduction in the presence of NADH. The potential fluorescence imaging of hypoxia based on NTR-mediated reduction of NIB is confirmed using in-vitro cell culture experiments using human breast cancer (MCF−7) cells, which displayed a significant change in the fluorescence colour and intensity at low NIB concentration within a short incubation period in hypoxic conditions. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10895-021-02800-6. Springer US 2021-08-12 2021 /pmc/articles/PMC8545720/ /pubmed/34383168 http://dx.doi.org/10.1007/s10895-021-02800-6 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Original Article Kumari, Rashmi R, Vasumathy Sunil, Dhanya Ningthoujam, Raghumani Singh Pandey, Badri Narain Kulkarni, Suresh D. Varadavenkatesan, Thivaharan Venkatachalam, Ganesh V, Anil Kumar N. A Nitronaphthalimide Probe for Fluorescence Imaging of Hypoxia in Cancer Cells |
title | A Nitronaphthalimide Probe for Fluorescence Imaging of Hypoxia in Cancer Cells |
title_full | A Nitronaphthalimide Probe for Fluorescence Imaging of Hypoxia in Cancer Cells |
title_fullStr | A Nitronaphthalimide Probe for Fluorescence Imaging of Hypoxia in Cancer Cells |
title_full_unstemmed | A Nitronaphthalimide Probe for Fluorescence Imaging of Hypoxia in Cancer Cells |
title_short | A Nitronaphthalimide Probe for Fluorescence Imaging of Hypoxia in Cancer Cells |
title_sort | nitronaphthalimide probe for fluorescence imaging of hypoxia in cancer cells |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8545720/ https://www.ncbi.nlm.nih.gov/pubmed/34383168 http://dx.doi.org/10.1007/s10895-021-02800-6 |
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