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Australian Journal of Chemistry Australian Journal of Chemistry Society
An international journal for chemical science
RESEARCH ARTICLE

Natural Product-Inspired Pyranonaphthoquinone Inhibitors of Indoleamine 2,3-Dioxygenase-1 (IDO-1)*

David J. A. Bridewell A , Jonathan Sperry B , Jason R. Smith C , Priambudi Kosim-Satyaputra C , Lai-Ming Ching A , Joanne F. Jamie C and Margaret A. Brimble B D

A Auckland Cancer Society Research Centre, Faculty of Medical and Health Sciences, The University of Auckland, Auckland Central 1010, New Zealand.

B School of Chemical Sciences, The University of Auckland, Auckland Central 1010, New Zealand.

C Department of Chemistry and Biomolecular Sciences, Macquarie University, Sydney, NSW 2109, Australia.

D Corresponding author. Email: m.brimble@auckland.ac.nz

Australian Journal of Chemistry 66(1) 40-49 http://dx.doi.org/10.1071/CH12393
Submitted: 23 August 2012  Accepted: 29 October 2012   Published: 12 November 2012

Abstract

A series of pyranonaphthoquinone derivatives possessing structural features present in both natural products annulin B and exiguamine A have been shown to exhibit low micromolar inhibition of indoleamine 2,3-dioxygenase-1 (IDO-1). These inhibitors retain activity against the enzyme in a cellular context with an approximate one-log loss of dose potency against IDO-1 in cells. One particular analogue, triazole 8 shows good inhibition of IDO-1 along with little loss of cell viability at low drug concentrations. These results have extended the naphthoquinone series of novel IDO-1 inhibitors based on lead compounds from nature.

Graphical Abstract Image


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