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Table of Contents
Vol. 46, No. 1, 2000
Issue release date: January – February
Section title: Microbiology
Chemotherapy 2000;46:43–48
(DOI:10.1159/000007255)

In vitro Investigation of the Antimicrobial Activities of Novel Tetramethylpiperidine- Substituted Phenazines against Mycobacterium tuberculosis

van Rensburg C.E.J.a · Jooné G.K.a · Sirgel F.A.b · Matlola N.M.a · O’Sullivan J.F.c
aMedical Research Council Unit for Inflammation and Immunity, Department of Immunology, Institute for Pathology, Faculty of Medicine, University of Pretoria, bNational Tuberculosis Research Programme, Medical Research Council, Tygerberg, South Africa; cDepartment of Chemistry, University College Belfield, Dublin, Ireland

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Article / Publication Details

First-Page Preview
Abstract of Microbiology

Published online: December 24, 1999
Issue release date: January – February

Number of Print Pages: 6
Number of Figures: 2
Number of Tables: 2

ISSN: 0009-3157 (Print)
eISSN: 1421-9794 (Online)

For additional information: http://www.karger.com/CHE

Abstract

The intra- and extracellular activities of 5 novel tetramethylpiperidine (TMP)-substituted phenazines against Mycobacterium tuberculosis H37Rv (ATCC 27294) were determined and compared with those of clofazimine and rifampicin. Two of these agents, together with clofazimine, were also tested for their activities against drug-resistant strains of M. tuberculosis. Three of the TMP-substituted phenazine compounds were significantly more active than clofazimine against M. tuberculosis, including multidrug-resistant clinical strains of this microbial pathogen, demonstrating a lack of cross-resistance between the riminophenazines and standard anti-tuberculous drugs. Using M. tuberculosis-infected monocyte-derived macrophages, all of the TMP-substituted phenazines were found to possess intracellular activity which was superior to that of both clofazimine and rifampicin. In this model of intracellular bioactivity, the experimental compounds inhibited bacterial growth at concentrations which were approximately 10-fold lower than the corresponding minimal inhibitory concentration values obtained using conventional in vitro sensitivity testing procedures. These results demonstrate that the novel TMP phenazines are active against multidrug-resistant M. tuberculosis strains, and particularly effective intracellularly.

© 2000 S. Karger AG, Basel


Article / Publication Details

First-Page Preview
Abstract of Microbiology

Published online: December 24, 1999
Issue release date: January – February

Number of Print Pages: 6
Number of Figures: 2
Number of Tables: 2

ISSN: 0009-3157 (Print)
eISSN: 1421-9794 (Online)

For additional information: http://www.karger.com/CHE


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Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
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