Activity of phenazine analogs against Mycobacterium leprae infections in mice. 1993

R M Van Landingham, and L L Walker, and J F O'Sullivan, and T M Shinnick
Division of Bacterial and Mycotic Diseases, Centers for Disease Control, Atlanta, Georgia 30333.

Twenty-five compounds structurally related to clofazimine were tested for their ability to inhibit the growth of Mycobacterium leprae using the kinetic method of drug evaluation in the mouse foot pad model of leprosy. Seven of the phenazine derivatives displayed anti-M. leprae activity comparable to that of clofazimine when administered at a concentration of 0.01% (w/w) in the diet. Three of the compounds, B746, B4087, and B4101, were active when administered at 0.001% in the diet. At a dietary concentration of 0.0001%, B4087 and B4101 were slightly more active than clofazimine, while B746 was less active. In the kinetic method of drug evaluation, greater anti-M. leprae activity of phenazine derivatives was generally associated with greater pigmentation of abdominal fat. Of the compounds which did not cause pigmentation when fed at a concentration of 0.01% in the diet B4090 was the most active. This compound also inhibits the growth of a clofazimine-resistant M. smegmatis strain.

UI MeSH Term Description Entries
D007700 Kinetics The rate dynamics in chemical or physical systems.
D007918 Leprosy A chronic granulomatous infection caused by MYCOBACTERIUM LEPRAE. The granulomatous lesions are manifested in the skin, the mucous membranes, and the peripheral nerves. Two polar or principal types are lepromatous and tuberculoid. Hansen's Disease,Hansen Disease
D009166 Mycobacterium leprae A species of gram-positive, aerobic bacteria that causes LEPROSY in man. Its organisms are generally arranged in clumps, rounded masses, or in groups of bacilli side by side.
D010619 Phenazines
D010858 Pigmentation Coloration or discoloration of a part by a pigment. Pigmentations
D002991 Clofazimine A fat-soluble riminophenazine dye used for the treatment of leprosy. It has been used investigationally in combination with other antimycobacterial drugs to treat Mycobacterium avium infections in AIDS patients. Clofazimine also has a marked anti-inflammatory effect and is given to control the leprosy reaction, erythema nodosum leprosum. (From AMA Drug Evaluations Annual, 1993, p1619) B-663,G-30,320,Lamprene,N,5-Bis(4-chlorophenyl)-3,5-dihydro-3-((1-methylethyl)imino)-2-phenazinamine,B 663,B663,G 30,320,G30,320
D004195 Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases. Animal Disease Model,Animal Disease Models,Disease Model, Animal
D004353 Drug Evaluation, Preclinical Preclinical testing of drugs in experimental animals or in vitro for their biological and toxic effects and potential clinical applications. Drug Screening,Evaluation Studies, Drug, Pre-Clinical,Drug Evaluation Studies, Preclinical,Drug Evaluations, Preclinical,Evaluation Studies, Drug, Preclinical,Evaluation, Preclinical Drug,Evaluations, Preclinical Drug,Medicinal Plants Testing, Preclinical,Preclinical Drug Evaluation,Preclinical Drug Evaluations,Drug Screenings,Screening, Drug,Screenings, Drug
D005260 Female Females
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man

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