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Sidechain Diversification of Grandifloracin Allows Identification of Analogues with Enhanced Anti‐Austerity Activity against Human PANC‐1 Pancreatic Cancer Cells
- Source :
- Chemmedchem, Alexander, B E, Sun, S, Palframan, M J, Kociok-Köhn, G, Dibwe, D F, Watanabe, S, Caggiano, L, Awale, 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, vol. 15, no. 1, pp. 125-135 . https://doi.org/10.1002/cmdc.201900549
- Publication Year :
- 2019
- Publisher :
- Wiley, 2019.
-
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.<br />Austerity measures: Grandifloracin is a natural product that is known to exhibit anti‐austerity activity, i. e. it is able to abolish the ability of pancreatic cancer cells to survive under “austere” conditions of nutrient deprivation. Herein we report the synthesis and biological evaluation of analogues of grandifloracin, as well as our findings on rearrangement and fragmentation reactions of the dimeric grandifloracin core. Live imaging, fluorescence microscopy and colony formation experiments with the most active analogue are described.
- Subjects :
- Bridged-Ring Compounds
Cancer chemotherapy
Cell Survival
antiproliferation
Grandifloracin
Molecular Conformation
Crystallography, X-Ray
01 natural sciences
Biochemistry
Pharmacology, Toxicology and Pharmaceutics(all)
chemistry.chemical_compound
SDG 3 - Good Health and Well-being
Cell Line, Tumor
Pancreatic cancer
Drug Discovery
medicine
Humans
cancer
Potency
General Pharmacology, Toxicology and Pharmaceutics
Pharmacology
Biological Products
dimerization
Natural product
Full Paper
010405 organic chemistry
Organic Chemistry
Cancer
Stereoisomerism
Biological activity
Full Papers
medicine.disease
Antineoplastic Agents, Phytogenic
dearomatization
0104 chemical sciences
Pancreatic Neoplasms
010404 medicinal & biomolecular chemistry
nutrient deprivation
chemistry
Pancreatic cancer cell
Molecular Medicine
Subjects
Details
- ISSN :
- 18607187 and 18607179
- Volume :
- 15
- Database :
- OpenAIRE
- Journal :
- ChemMedChem
- Accession number :
- edsair.doi.dedup.....6dde50f906d219ad6ba512426440165f