Sidechain diversification of grandifloracin allows identification of analogues with enhanced anti-austerity activity against human PANC-1 pancreatic cancer cells
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
MetadataShow full item record
Abstract© 2019 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. 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.
CitationAlexander, B. E., Sun, S., Palframan, M. J., Kociok‐Köhn, G., Dibwe, D. F., Watanabe, S., Caggiano, L., Awale, S. and Lewis, S. E. (2019) Sidechain diversification of grandifloracin allows identification of analogues with enhanced anti-austerity activity against human PANC-1 pancreatic cancer cells, ChemMedChem, 15, pp. 125-135.
SponsorsWe thank EPSRC (DTP studentship to B.E.A.) and Cancer Research at Bath (CR@B) for funding. The biological investigation was supported by a grant from the Japanese Society for the Promotion of Science (JSPS Kakenhi #16 K08319) and the Kobayashi International Scholarship Foundation to S.A.
Except where otherwise noted, this item's license is described as https://creativecommons.org/licenses/by/4.0/
- The enone motif of (+)-grandifloracin is not essential for 'anti-austerity' antiproliferative activity.
- Authors: Ali Khan M, Wood PJ, Lamb-Guhren NM, Caggiano L, Kociok-Köhn G, Tosh D, Lewis SE
- Issue date: 2014 Jul 1
- Antiausterity agents from Uvaria dac and their preferential cytotoxic activity against human pancreatic cancer cell lines in a nutrient-deprived condition.
- Authors: Awale S, Ueda JY, Athikomkulchai S, Abdelhamed S, Yokoyama S, Saiki I, Miyatake R
- Issue date: 2012 Jun 22
- Exceedingly Efficient Synthesis of (±)-Grandifloracin and Acylated Analogues.
- Authors: Bergner M, Duquette DC, Chio L, Stoltz BM
- Issue date: 2015 Jun 19
- Evaluation of synthetic coumarins for antiausterity cytotoxicity against pancreatic cancers.
- Authors: Farley CM, Dibwe DF, Ueda JY, Hall EA, Awale S, Magolan J
- Issue date: 2016 Mar 1
- A synthetic approach to novel carvotacetone and antheminone analogues with anti-tumour activity.
- Authors: Christou S, Ozturk E, Pritchard RG, Quayle P, Stratford IJ, Whitehead RC, Williams KF
- Issue date: 2013 Sep 15