Studies for the elucidation of the mode of action of the antimycotic hydroxypyridone compound, rilopirox.
Rilopirox is a synthetic, fungicidal antimycotic agent with hydrophobic characteristics. Its chemical name is 6-[4-(4-chlorophenoxy)-phenoxy-methyl]-1-hydroxy-4-methyl-2-pyridone and it has a molecular weight of 357.79. Rilopirox is very soluble in dimethyl sulfoxide (DMSO) and dimethylformamide (DMF) but poorly soluble in water. The amount of antimycotic agent remaining in the solution is dependent on the final concentration of the solvent and the amount of rilopirox used. Complexometric studies show that rilopirox has a high affinity for iron ions [unpubl. data]. Catalase, an iron-containing enzyme, is inhibited by the chelating agent rilopirox. Studies on yeast mitochondria and submitochondrial particles show that rilopirox inhibits the respiratory chain. Complex I (NADH-ubiquinone oxidoreductase) contains iron-sulfur proteins and is the main system which is inhibited.
Kruse
R
R
Ruhr-University, Bochum, FRG.
Hengstenberg
W
W
Hänel
H
H
Raether
W
W
D000935:Antifungal Agents / Q000737:chemistry / Q000494:pharmacology*; D002374:Catalase / Q000037:antagonists & inhibitors; D002614:Chelating Agents / Q000494:pharmacology; D004579:Electron Transport / Q000187:drug effects; D042963:Electron Transport Complex II; D014450:Electron Transport Complex III / Q000037:antagonists & inhibitors; D007502:Iron Chelating Agents; D008928:Mitochondria / Q000187:drug effects; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000037:antagonists & inhibitors; D010088:Oxidoreductases / Q000037:antagonists & inhibitors; D011728:Pyridones / Q000737:chemistry / Q000494:pharmacology*; D012441:Saccharomyces cerevisiae / Q000187:drug effects; D012995:Solubility; D013347:Subcellular Fractions / Q000187:drug effects; D013385:Succinate Dehydrogenase / Q000037:antagonists & inhibitors
D000935:Antifungal Agents; D002614:Chelating Agents; D007502:Iron Chelating Agents; D009097:Multienzyme Complexes; D011728:Pyridones; C066307:rilopirox; D010088:Oxidoreductases; D002374:Catalase; D042963:Electron Transport Complex II; D013385:Succinate Dehydrogenase; D016660:NAD(P)H Dehydrogenase (Quinone); D014450:Electron Transport Complex III