NEW YORK (Reuters Health) - Antimycobacterial calixarenes enhance innate defense mechanisms against Mycobacterium tuberculosis infection in mice, according to a report in the November issue of Infection and Immunity.
“New therapeutic agents against tuberculosis, with activity mediated through host-derived effector mechanisms, could be particularly attractive, since they could be less susceptible to selection for drug resistance,” Dr. Ricardo E. Tascon from The National Institute for Medical Research, London, told Reuters Health.
Dr. Tascon and colleagues studied the effectiveness of the calixarene Macrocyclon and several structurally related calixarenes in controlling M. tuberculosis infection in mice and investigated its mechanism of action.
Macrocyclon-treated mice infected with M. tuberculosis had significantly lower numbers of viable M. tuberculosis in the spleen and lungs, the authors report.
Similar antimycobacterial effects were demonstrated in mice lacking conventional CD4+ T cells and in athymic mice lacking both CD4+ and CD8+ T cells, the results indicate.
Three calixarenes besides Macrocyclon also induced significant antimycobacterial activities in mice, the researchers note.
In macrophage cultures, calixarene-induced antimycobacterial activity required the presence of L-arginine and inducible nitric oxide synthase, the report indicates.
“At present, it is not known whether Macrocyclon has any effects on other bacterial species,” the authors note. “Similarly, a fundamental priority will be to investigate whether Macrocyclon is also effective in controlling mycobacterial infections by human macrophages.”
“Our work aims at developing novel adjunctive therapies for tuberculosis control,” Dr. Tascon said. “We are concentrated in studying in more detail the mechanisms of action of the new calixarene compounds.”
Source: Infect Immun 2004;72:6318-6323. [ Google search on this article ]
MeSH Headings:Animal Diseases: Disease Models, Animal: Drugs, Investigational: DiseasesCopyright © 2002 Reuters Limited. All rights reserved. Republication or redistribution of Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Reuters and the Reuters sphere logo are registered trademarks and trademarks of the Reuters group of companies around the world.
