Premium
Sidechain Diversification of Grandifloracin Allows Identification of Analogues with Enhanced Anti‐Austerity Activity against Human PANC‐1 Pancreatic Cancer Cells
Author(s) -
Alexander Benjamin E.,
Sun Sijia,
Palframan Matthew J.,
KociokKöhn Gabriele,
Dibwe Dya Fita,
Watanabe Shiro,
Caggiano Lorenzo,
Awale Suresh,
Lewis Simon E.
Publication year - 2020
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201900549
Subject(s) - austerity , pancreatic cancer , natural product , biological activity , potency , cancer cell lines , cell culture , chemistry , cancer research , cancer , cancer cell , biology , biochemistry , in vitro , genetics , politics , political science , law
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.