title: Activity of phenazine analogs against Mycobacterium leprae infections in mice.
abstract: 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.
authors.affiliation: Division of Bacterial and Mycotic Diseases, Centers for Disease Control, Atlanta, Georgia 30333.
authors.forename: R M
authors.initials: RM
authors.lastname: Van Landingham
authors.forename: L L
authors.initials: LL
authors.lastname: Walker
authors.forename: J F
authors.initials: JF
authors.lastname: O'Sullivan
authors.forename: T M
authors.initials: TM
authors.lastname: Shinnick
mesh_terms: D000005:Abdomen; D000273:Adipose Tissue / Q000187:drug effects; D000818:Animals; D002991:Clofazimine / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D005260:Female; D006801:Humans; D007700:Kinetics; D007918:Leprosy / Q000188:drug therapy* / Q000382:microbiology; D051379:Mice; D015394:Molecular Structure; D009166:Mycobacterium leprae / Q000187:drug effects* / Q000254:growth & development; D010619:Phenazines / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D010858:Pigmentation
chemical_list: D010619:Phenazines; D002991:Clofazimine