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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Detalles Bibliográficos
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:
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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
Descripción
Sumario: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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