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Polygodial and Ophiobolin A Analogues for Covalent Crosslinking of Anticancer Targets
In a search of small molecules active against apoptosis-resistant cancer cells, including glioma, melanoma, and non-small cell lung cancer, we previously prepared α,β- and γ,δ-unsaturated ester analogues of polygodial and ophiobolin A, compounds capable of pyrrolylation of primary amines and demonst...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8537666/ https://www.ncbi.nlm.nih.gov/pubmed/34681916 http://dx.doi.org/10.3390/ijms222011256 |
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author | Maslivetc, Vladimir Laguera, Breana Chandra, Sunena Dasari, Ramesh Olivier, Wesley J. Smith, Jason A. Bissember, Alex C. Masi, Marco Evidente, Antonio Mathieu, Veronique Kornienko, Alexander |
author_facet | Maslivetc, Vladimir Laguera, Breana Chandra, Sunena Dasari, Ramesh Olivier, Wesley J. Smith, Jason A. Bissember, Alex C. Masi, Marco Evidente, Antonio Mathieu, Veronique Kornienko, Alexander |
author_sort | Maslivetc, Vladimir |
collection | PubMed |
description | In a search of small molecules active against apoptosis-resistant cancer cells, including glioma, melanoma, and non-small cell lung cancer, we previously prepared α,β- and γ,δ-unsaturated ester analogues of polygodial and ophiobolin A, compounds capable of pyrrolylation of primary amines and demonstrating double-digit micromolar antiproliferative potencies in cancer cells. In the current work, we synthesized dimeric and trimeric variants of such compounds in an effort to discover compounds that could crosslink biological primary amine containing targets. We showed that such compounds retain the pyrrolylation ability and possess enhanced single-digit micromolar potencies toward apoptosis-resistant cancer cells. Target identification studies of these interesting compounds are underway. |
format | Online Article Text |
id | pubmed-8537666 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-85376662021-10-24 Polygodial and Ophiobolin A Analogues for Covalent Crosslinking of Anticancer Targets Maslivetc, Vladimir Laguera, Breana Chandra, Sunena Dasari, Ramesh Olivier, Wesley J. Smith, Jason A. Bissember, Alex C. Masi, Marco Evidente, Antonio Mathieu, Veronique Kornienko, Alexander Int J Mol Sci Communication In a search of small molecules active against apoptosis-resistant cancer cells, including glioma, melanoma, and non-small cell lung cancer, we previously prepared α,β- and γ,δ-unsaturated ester analogues of polygodial and ophiobolin A, compounds capable of pyrrolylation of primary amines and demonstrating double-digit micromolar antiproliferative potencies in cancer cells. In the current work, we synthesized dimeric and trimeric variants of such compounds in an effort to discover compounds that could crosslink biological primary amine containing targets. We showed that such compounds retain the pyrrolylation ability and possess enhanced single-digit micromolar potencies toward apoptosis-resistant cancer cells. Target identification studies of these interesting compounds are underway. MDPI 2021-10-19 /pmc/articles/PMC8537666/ /pubmed/34681916 http://dx.doi.org/10.3390/ijms222011256 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Communication Maslivetc, Vladimir Laguera, Breana Chandra, Sunena Dasari, Ramesh Olivier, Wesley J. Smith, Jason A. Bissember, Alex C. Masi, Marco Evidente, Antonio Mathieu, Veronique Kornienko, Alexander Polygodial and Ophiobolin A Analogues for Covalent Crosslinking of Anticancer Targets |
title | Polygodial and Ophiobolin A Analogues for Covalent Crosslinking of Anticancer Targets |
title_full | Polygodial and Ophiobolin A Analogues for Covalent Crosslinking of Anticancer Targets |
title_fullStr | Polygodial and Ophiobolin A Analogues for Covalent Crosslinking of Anticancer Targets |
title_full_unstemmed | Polygodial and Ophiobolin A Analogues for Covalent Crosslinking of Anticancer Targets |
title_short | Polygodial and Ophiobolin A Analogues for Covalent Crosslinking of Anticancer Targets |
title_sort | polygodial and ophiobolin a analogues for covalent crosslinking of anticancer targets |
topic | Communication |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8537666/ https://www.ncbi.nlm.nih.gov/pubmed/34681916 http://dx.doi.org/10.3390/ijms222011256 |
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