Sidechain diversification of grandifloracin allows identification of analogues with enhanced anti-austerity activity against human PANC-1 pancreatic cancer cells
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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.
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