Sidechain Diversification of Grandifloracin Allows Identification of Analogues with Enhanced Anti‐Austerity Activity against Human PANC‐1 Pancreatic Cancer Cells

The natural product (+)‐grandifloracin is a potent “anti‐austerity” agent, able to suppress the ability of various pancreatic cancer cell lines to tolerate conditions of nutrient deprivation. Such anti‐austerity agents represent a promising approach to cancer chemotherapy. Here we report the synthes...

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Autores principales: Alexander, Benjamin E., Sun, Sijia, Palframan, Matthew J., Kociok‐Köhn, Gabriele, Dibwe, Dya Fita, Watanabe, Shiro, Caggiano, Lorenzo, Awale, Suresh, Lewis, Simon E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
Materias:
Full Papers
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7003952/
https://www.ncbi.nlm.nih.gov/pubmed/31821731
http://dx.doi.org/10.1002/cmdc.201900549
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author Alexander, Benjamin E.
Sun, Sijia
Palframan, Matthew J.
Kociok‐Köhn, Gabriele
Dibwe, Dya Fita
Watanabe, Shiro
Caggiano, Lorenzo
Awale, Suresh
Lewis, Simon E.
author_facet Alexander, Benjamin E.
Sun, Sijia
Palframan, Matthew J.
Kociok‐Köhn, Gabriele
Dibwe, Dya Fita
Watanabe, Shiro
Caggiano, Lorenzo
Awale, Suresh
Lewis, Simon E.
author_sort Alexander, Benjamin E.
collection PubMed
description The natural product (+)‐grandifloracin is a potent “anti‐austerity” agent, able to suppress the ability of various pancreatic cancer cell lines to tolerate conditions of nutrient deprivation. Such anti‐austerity agents represent a promising approach to cancer chemotherapy. Here we report the synthesis and biological evaluation of racemic analogues of grandifloracin bearing diverse sidechains, of which two show enhanced potency in comparison with the natural product. Additionally, several unexpected by‐products containing modifications of the grandifloracin core were isolated, identified and similarly evaluated for biological activity.
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spelling pubmed-70039522020-02-11 Sidechain Diversification of Grandifloracin Allows Identification of Analogues with Enhanced Anti‐Austerity Activity against Human PANC‐1 Pancreatic Cancer Cells Alexander, Benjamin E. Sun, Sijia Palframan, Matthew J. Kociok‐Köhn, Gabriele Dibwe, Dya Fita Watanabe, Shiro Caggiano, Lorenzo Awale, Suresh Lewis, Simon E. ChemMedChem Full Papers The natural product (+)‐grandifloracin is a potent “anti‐austerity” agent, able to suppress the ability of various pancreatic cancer cell lines to tolerate conditions of nutrient deprivation. Such anti‐austerity agents represent a promising approach to cancer chemotherapy. Here we report the synthesis and biological evaluation of racemic analogues of grandifloracin bearing diverse sidechains, of which two show enhanced potency in comparison with the natural product. Additionally, several unexpected by‐products containing modifications of the grandifloracin core were isolated, identified and similarly evaluated for biological activity. John Wiley and Sons Inc. 2019-12-10 2020-01-07 /pmc/articles/PMC7003952/ /pubmed/31821731 http://dx.doi.org/10.1002/cmdc.201900549 Text en © 2019 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Full Papers
Alexander, Benjamin E.
Sun, Sijia
Palframan, Matthew J.
Kociok‐Köhn, Gabriele
Dibwe, Dya Fita
Watanabe, Shiro
Caggiano, Lorenzo
Awale, Suresh
Lewis, Simon E.
Sidechain Diversification of Grandifloracin Allows Identification of Analogues with Enhanced Anti‐Austerity Activity against Human PANC‐1 Pancreatic Cancer Cells
title Sidechain Diversification of Grandifloracin Allows Identification of Analogues with Enhanced Anti‐Austerity Activity against Human PANC‐1 Pancreatic Cancer Cells
title_full Sidechain Diversification of Grandifloracin Allows Identification of Analogues with Enhanced Anti‐Austerity Activity against Human PANC‐1 Pancreatic Cancer Cells
title_fullStr Sidechain Diversification of Grandifloracin Allows Identification of Analogues with Enhanced Anti‐Austerity Activity against Human PANC‐1 Pancreatic Cancer Cells
title_full_unstemmed Sidechain Diversification of Grandifloracin Allows Identification of Analogues with Enhanced Anti‐Austerity Activity against Human PANC‐1 Pancreatic Cancer Cells
title_short Sidechain Diversification of Grandifloracin Allows Identification of Analogues with Enhanced Anti‐Austerity Activity against Human PANC‐1 Pancreatic Cancer Cells
title_sort sidechain diversification of grandifloracin allows identification of analogues with enhanced anti‐austerity activity against human panc‐1 pancreatic cancer cells
topic Full Papers
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7003952/
https://www.ncbi.nlm.nih.gov/pubmed/31821731
http://dx.doi.org/10.1002/cmdc.201900549
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