Inhibition of H(+)-ATPase-mediated proton pumping in Cryptococcus neoformans by a novel conjugated styryl ketone.
We investigated the in vitro susceptibility of clinical isolates of Cryptococcus neoformans to the novel conjugated styryl ketone NC1175 by broth microdilution. The MIC(90) and the MFC of NC1175 for C. neoformans were 1 and 2 mg/L, respectively. NC1175 at low concentrations (1-4 mg/L) completely inhibited the glucose-induced acidification of the external medium caused by the extrusion of intracellular protons mediated by the plasma membrane located H(+)-ATPase. These data suggest that NC1175 is a fungicidal agent for C. neoformans and its possible cellular target(s) include the H(+)-ATPase.
Division of Infectious Diseases, Department of Internal Medicine, 427 Lande Building, Wayne State University, 550 E. Canfield, Detroit, MI 48201, USA. aa1388@wayne.edu
E K
EK
Manavathu
J R
JR
Dimmock
S C
SC
Vashishtha
P H
PH
Chandrasekar
D000935:Antifungal Agents / Q000494:pharmacology*; D002462:Cell Membrane / Q000201:enzymology; D003455:Cryptococcus neoformans / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008352:Mannich Bases / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D010880:Piperidines / Q000494:pharmacology*; D054328:Proton Pump Inhibitors; D017494:Proton Pumps / Q000378:metabolism; D006180:Proton-Translocating ATPases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013997:Time Factors
D000935:Antifungal Agents; D008352:Mannich Bases; C117532:NC 1175; D010880:Piperidines; D054328:Proton Pump Inhibitors; D017494:Proton Pumps; D006180:Proton-Translocating ATPases