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

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

Keywords

antiproliferation
cancer
dearomatization
dimerization
nutrient deprivation

ASJC Scopus subject areas

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

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10.1002/cmdc.201900549Licence: CC BY

___ChemMedChem__2020_15_125___Final published version, 2.55 MBLicence: CC BY

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1 Finished

Analogues for grandifloracin as “anti-austerity” agents for pancreatic cancer chemotherapy.
Lewis, S. & Whatmore, J.
1/09/15 → 2/11/15
Project: Research-related funding

Lorenzo Caggiano
- L.Caggiano@bath.ac.uk
- Department of Pharmacy & Pharmacology - Senior Lecturer
Person: Research & Teaching

MC2-Mass Spectrometry (MS)
Material and Chemical Characterisation (MC2)
Facility/equipment: Technology type
MC2- Nuclear Magnetic Resonance (NMR)
Material and Chemical Characterisation (MC2)
Facility/equipment: Technology type
MC2- X-ray diffraction (XRD)
Material and Chemical Characterisation (MC2)
Facility/equipment: Technology type

Cite this

Sidechain Diversification of Grandifloracin Allows Identification of Analogues with Enhanced Anti-Austerity Activity against Human PANC-1 Pancreatic Cancer Cells. / Alexander, Benjamin E.; Sun, Sijia; Palframan, Matthew J.; Kociok-Köhn, Gabriele; Dibwe, Dya Fita; Watanabe, Shiro; Caggiano, Lorenzo; Awale, Suresh; Lewis, Simon E.

In: ChemMedChem, Vol. 15, No. 1, 07.01.2020, p. 125-135.

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

Alexander, Benjamin E. ; Sun, Sijia ; Palframan, Matthew J. ; Kociok-Köhn, Gabriele ; Dibwe, Dya Fita ; Watanabe, Shiro ; Caggiano, Lorenzo ; Awale, Suresh ; Lewis, Simon E. / Sidechain Diversification of Grandifloracin Allows Identification of Analogues with Enhanced Anti-Austerity Activity against Human PANC-1 Pancreatic Cancer Cells. In: ChemMedChem. 2020 ; Vol. 15, No. 1. pp. 125-135.

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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.",

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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

Keywords

ASJC Scopus subject areas

Access to Document

Analogues for grandifloracin as “anti-austerity” agents for pancreatic cancer chemotherapy.

Lorenzo Caggiano

MC2-Mass Spectrometry (MS)

MC2- Nuclear Magnetic Resonance (NMR)

MC2- X-ray diffraction (XRD)

Cite this