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Infection and Immunity, November 2004, p. 6318-6323, Vol. 72, No. 11
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.11.6318-6323.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Antimycobacterial Calixarenes Enhance Innate Defense Mechanisms in Murine Macrophages and Induce Control of Mycobacterium tuberculosis Infection in Mice

M. Joseph Colston,1 Helen C. Hailes,2 Evangelos Stavropoulos,1 Anne C. Hervé,2 Gwenaelle Hervé,2 Kerry J. Goodworth,2 Alison M. Hill,3 Peter Jenner,1 Philip D. Hart,1 and Ricardo E. Tascon1*

The National Institute for Medical Research, The Ridgeway, Mill Hill,1 Department of Chemistry, University College London, London,2 School of Chemistry, University of Exeter, Exeter, United Kingdom3

Received 4 March 2004/ Returned for modification 6 May 2004/ Accepted 4 August 2004

Tuberculosis remains the leading cause of death among infectious diseases, accounting for more than two million deaths annually. The incidence of the disease is increasing globally, partially because of the resurgence of drug-resistant strains of Mycobacterium tuberculosis. Calixarenes are macrocyclic oligomers, some of which are able to modify the growth of M. tuberculosis in infected cells. Most experimental work has been carried out with Macrocyclon, also known as HOC 12.5EO. In this study, we demonstrate that Macrocyclon is effective in controlling M. tuberculosis infections, and we provide evidence that its effect is partially mediated by an L-arginine-dependent mechanism of macrophage activation that involves the activity of the inducible nitric oxide synthase. We also show that Macrocyclon is effective in athymic and major histocompatibility complex class II–/– mice and synthesized a number of structurally related calixarenes expressing significant antimycobacterial activity.

* Corresponding author. Mailing address: The National Institute for Medical Research, Mill Hill, London NW7 1AA, United Kingdom. Phone: 44 0 208 959 3666. Fax: 44 0 208 906 4477. E-mail: tricard{at}nimr.mrc.ac.uk.

Editor: S. H. E. Kaufmann

Infection and Immunity, November 2004, p. 6318-6323, Vol. 72, No. 11
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.11.6318-6323.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

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