Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 125-135 |
| Number of pages | 11 |
| Journal | ChemMedChem |
| Volume | 15 |
| Issue number | 1 |
| Early online date | 10 Dec 2019 |
| DOIs | |
| Publication status | Published - 7 Jan 2020 |
Keywords
- antiproliferation
- cancer
- dearomatization
- dimerization
- nutrient deprivation
ASJC Scopus subject areas
- Biochemistry
- Molecular Medicine
- Pharmacology
- Drug Discovery
- Pharmacology, Toxicology and Pharmaceutics(all)
- Organic Chemistry
Cite this
Alexander, B. E., Sun, S., Palframan, M. J., Kociok-Köhn, G., Dibwe, D. F., Watanabe, S., ... Lewis, S. E. (2020). Sidechain Diversification of Grandifloracin Allows Identification of Analogues with Enhanced Anti-Austerity Activity against Human PANC-1 Pancreatic Cancer Cells. ChemMedChem, 15(1), 125-135. https://doi.org/10.1002/cmdc.201900549