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Journal of Antimicrobial Chemotherapy (1999) 43, 615-623
© 1999 The British Society for Antimicrobial Chemotherapy

Review

Antimycobacterial activities of riminophenazines

Venkata M. Reddya, John F. O' Sullivanb and Pattisapu R. J. Gangadharamc,*

aDepartment of Biomedical Sciences, UIC College of Medicine at Rockford, Rockford, IL 61107, USA; bChemistry Department, University College of Dublin, Dublin, Republic of Ireland; cMycobacteriology Research Laboratories, Department of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA

Riminophenazines were specifically developed as drugs active against Mycobacterium tuberculosis but extensive research over several decades has shown that these compounds are also active against many other mycobacterial infections, particularly those caused by Mycobacterium leprae and the Mycobacterium aviumcomplex (MAC). Clofazimine, the lead compound in this series, is included in the regimens that are approved by the WHO for the treatment of leprosy and has contributed significantly to the control of that disease, particularly that caused by dapsone-resistant bacteria. Despite early problems, clofazimine has shown clinical efficacy in tuberculosis, in particular that caused by multiple drug resistant strains. Clofazimine does not induce resistance and also inhibits emergence of resistance to isoniazid in M. tuberculosis. The efficacy of clofazimine against MAC is more varied and the availability of better drugs has limited its use. Newer riminophenazines, such as B746 and B4157, not only showed increased anti-mycobacterial activity but also produced less skin pigmentation, which is the main drawback of this group of compounds. The most important virtues of riminophenazines, such as intracellular accumulation in mononuclear phagocytic cells, anti-inflammatory activity, a low incidence of drug resistance and slow metabolic elimination, make them attractive candidates for the treatment of mycobacterial infections. It is essential, however, to investigate the newer analogues clinically, while continuing the pursuit of alternate candidates that demonstrate higher anti-mycobacterial activity and lower rates of skin pigmentation.

* Corresponding author. Tel: +1-312-413-3099; Fax: +1-312-996-6099.


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