Sidechain Diversification of Grandifloracin Allows Identification of Analogues with Enhanced Anti-Austerity Activity against Human PANC-1 Pancreatic Cancer Cells

Benjamin E. Alexander; Sijia Sun; Matthew J. Palframan; Gabriele Kociok-Köhn; Dya Fita Dibwe; Shiro Watanabe; Lorenzo Caggiano; Suresh Awale; Simon E. Lewis

doi:10.1002/cmdc.201900549

Sidechain Diversification of Grandifloracin Allows Identification of Analogues with Enhanced Anti-Austerity Activity against Human PANC-1 Pancreatic Cancer Cells

Benjamin E. Alexander, Sijia Sun, Matthew J. Palframan, Gabriele Kociok-Köhn, Dya Fita Dibwe, Shiro Watanabe, Lorenzo Caggiano, Suresh Awale, Simon E. Lewis

University of Toyama

Research output: Contribution to journal › Article › peer-review

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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	https://doi.org/10.1002/cmdc.201900549
Publication status	Published - 7 Jan 2020

Bibliographical note

Keywords

antiproliferation
cancer
dearomatization
dimerization
nutrient deprivation

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Pharmacology
Drug Discovery
Pharmacology, Toxicology and Pharmaceutics(all)
Organic Chemistry

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1002/cmdc.201900549Licence: CC BY

___ChemMedChem__2020_15_125___Final published version, 2.55 MBLicence: CC BY

Cite this

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title = "Sidechain Diversification of Grandifloracin Allows Identification of Analogues with Enhanced Anti-Austerity Activity against Human PANC-1 Pancreatic Cancer Cells",

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.",

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AU - Kociok-Köhn, Gabriele

AU - Dibwe, Dya Fita

AU - Watanabe, Shiro

AU - Caggiano, Lorenzo

AU - Awale, Suresh

AU - Lewis, Simon E.

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KW - antiproliferation

KW - cancer

KW - dearomatization

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Sidechain Diversification of Grandifloracin Allows Identification of Analogues with Enhanced Anti-Austerity Activity against Human PANC-1 Pancreatic Cancer Cells

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

Fingerprint

Lorenzo Caggiano

Avance 300 MHz Nuclear Magnetic Resonance (NMR) Spectrometer (1South)

Avance NEO 500 MHz Nuclear Magnetic Resonance (NMR) Spectrometer (1South)

Electrospray Time-of-Flight Mass Spectrometer (Open-Access)

Cite this

Sidechain Diversification of Grandifloracin Allows Identification of Analogues with Enhanced Anti-Austerity Activity against Human PANC-1 Pancreatic Cancer Cells

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

Fingerprint

Profiles

Lorenzo Caggiano

Equipment

Avance 300 MHz Nuclear Magnetic Resonance (NMR) Spectrometer (1South)

Avance NEO 500 MHz Nuclear Magnetic Resonance (NMR) Spectrometer (1South)

Electrospray Time-of-Flight Mass Spectrometer (Open-Access)

Cite this