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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
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.
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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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