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One-pot synthesis of cyclic-aminotropiminium carboxylate derivatives with DNA binding and anticancer properties

Tropolone, a nonbenzenoid aromatic molecule, is a constituent of troponoid natural products possessing a wide range of bioactivities, including anticancer. This report describes the one-pot synthesis and mechanistic studies of fifteen fluorescent C(aryl)-N(alkyl)-substituted cyclic-aminotroponiminiu...

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Autores principales: Palai, Bibhuti Bhusana, Patel, Saket Awadhesbhai, Sharma, Nagendra K., Dixit, Manjusha
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9814901/
https://www.ncbi.nlm.nih.gov/pubmed/36697960
http://dx.doi.org/10.1038/s42004-022-00798-x
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author Palai, Bibhuti Bhusana
Patel, Saket Awadhesbhai
Sharma, Nagendra K.
Dixit, Manjusha
author_facet Palai, Bibhuti Bhusana
Patel, Saket Awadhesbhai
Sharma, Nagendra K.
Dixit, Manjusha
author_sort Palai, Bibhuti Bhusana
collection PubMed
description Tropolone, a nonbenzenoid aromatic molecule, is a constituent of troponoid natural products possessing a wide range of bioactivities, including anticancer. This report describes the one-pot synthesis and mechanistic studies of fifteen fluorescent C(aryl)-N(alkyl)-substituted cyclic-aminotroponiminium carboxylate (cATC) derivatives by unusual cycloaddition and rearrangement reactions. Herein, the biochemical studies of four cATC derivatives reveal a non-intercalative binding affinity with DNA duplex. In vitro/in vivo studies show strong anti-tumor activity in three cATC derivatives. These derivatives enter the cells and localize to the nucleus and cytoplasm, which are easily traceable due to their inherent fluorescence properties. These three cATC derivatives reduce the proliferation and migration of HeLa cells more than the non-cancer cell line. They induce p38-p53-mediated apoptosis and inhibit EMT. In xenograft-based mouse models, these cATC derivatives reduce tumor size. Overall, this study reports the synthesis of DNA binding fluorescent C(aryl)-N(alkyl)-cyclic-aminotroponiminium derivatives which show anti-tumor activity with the minimum side effect.
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spelling pubmed-98149012023-01-10 One-pot synthesis of cyclic-aminotropiminium carboxylate derivatives with DNA binding and anticancer properties Palai, Bibhuti Bhusana Patel, Saket Awadhesbhai Sharma, Nagendra K. Dixit, Manjusha Commun Chem Article Tropolone, a nonbenzenoid aromatic molecule, is a constituent of troponoid natural products possessing a wide range of bioactivities, including anticancer. This report describes the one-pot synthesis and mechanistic studies of fifteen fluorescent C(aryl)-N(alkyl)-substituted cyclic-aminotroponiminium carboxylate (cATC) derivatives by unusual cycloaddition and rearrangement reactions. Herein, the biochemical studies of four cATC derivatives reveal a non-intercalative binding affinity with DNA duplex. In vitro/in vivo studies show strong anti-tumor activity in three cATC derivatives. These derivatives enter the cells and localize to the nucleus and cytoplasm, which are easily traceable due to their inherent fluorescence properties. These three cATC derivatives reduce the proliferation and migration of HeLa cells more than the non-cancer cell line. They induce p38-p53-mediated apoptosis and inhibit EMT. In xenograft-based mouse models, these cATC derivatives reduce tumor size. Overall, this study reports the synthesis of DNA binding fluorescent C(aryl)-N(alkyl)-cyclic-aminotroponiminium derivatives which show anti-tumor activity with the minimum side effect. Nature Publishing Group UK 2022-12-27 /pmc/articles/PMC9814901/ /pubmed/36697960 http://dx.doi.org/10.1038/s42004-022-00798-x Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Palai, Bibhuti Bhusana
Patel, Saket Awadhesbhai
Sharma, Nagendra K.
Dixit, Manjusha
One-pot synthesis of cyclic-aminotropiminium carboxylate derivatives with DNA binding and anticancer properties
title One-pot synthesis of cyclic-aminotropiminium carboxylate derivatives with DNA binding and anticancer properties
title_full One-pot synthesis of cyclic-aminotropiminium carboxylate derivatives with DNA binding and anticancer properties
title_fullStr One-pot synthesis of cyclic-aminotropiminium carboxylate derivatives with DNA binding and anticancer properties
title_full_unstemmed One-pot synthesis of cyclic-aminotropiminium carboxylate derivatives with DNA binding and anticancer properties
title_short One-pot synthesis of cyclic-aminotropiminium carboxylate derivatives with DNA binding and anticancer properties
title_sort one-pot synthesis of cyclic-aminotropiminium carboxylate derivatives with dna binding and anticancer properties
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9814901/
https://www.ncbi.nlm.nih.gov/pubmed/36697960
http://dx.doi.org/10.1038/s42004-022-00798-x
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