title: Antimycobacterial action of B4128, a novel tetramethylpiperidyl-substituted phenazine.
abstract: The effects of the novel tetramethylpiperidyl (TMP)-substituted phenazine, B4128 (0.6-2.5 mg/L), on growth, phospholipase A2(PLA2) activity, cation (K+, Ca2+) fluxes and energy metabolism (ATP) of Mycobacterium aurum A(+) and Mycobacterium tuberculosis (H37Ra) have been investigated in vitro. Growth, PLA2 and cation fluxes were measured radiometrically, while microbial ATP was assayed by means of a luciferin/luciferase chemiluminescence method. Exposure of the mycobacteria to B4128 resulted in immediate, dose-related enhancement of microbial PLA2 activity and inhibition of K+ influx, which preceded effects on microbial ATP, influx of Ca2+ and growth. These results demonstrate that B4128 possesses membrane-directed antimycobacterial properties that are similar to those of clofazimine.
authors.affiliation: Medical Research Council Unit for Inflammation and Immunity, Department of Immunology, Institute for Pathology, University of Pretoria, PO Box 2034, Pretoria 0001, South Africa.
authors.forename: N M
authors.initials: NM
authors.lastname: Matlola
authors.forename: H C
authors.initials: HC
authors.lastname: Steel
authors.forename: R
authors.initials: R
authors.lastname: Anderson
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002132:Calcium Radioisotopes; D007202:Indicators and Reagents; D008826:Microbial Sensitivity Tests; D009161:Mycobacterium / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D010619:Phenazines / Q000494:pharmacology*; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D010880:Piperidines / Q000494:pharmacology*; D011188:Potassium / Q000378:metabolism; D012414:Rubidium Radioisotopes
chemical_list: C427405:3-(2,4-dichloroanilino)-10-(2,4-dichlorophenyl)-2,10-dihydro-2-(2,2,6,6 tetramethylpiperid-4-ylimino)phenazine; D000900:Anti-Bacterial Agents; D002132:Calcium Radioisotopes; D007202:Indicators and Reagents; D010619:Phenazines; D010880:Piperidines; D012414:Rubidium Radioisotopes; D000255:Adenosine Triphosphate; D010741:Phospholipases A; D054467:Phospholipases A2; D011188:Potassium; D002118:Calcium