[CAS NO. 29342-05-0]  Ciclopirox

Ciclopirox olamine (CPX) is a lipophilic bidentate iron chelator that stabilizes HIF-1alpha under normoxic conditions at lower concentrations than other iron chelators, probably by inhibiting HIF-1alpha hydroxylation. Ciclopirox olamine (CPX)-induced HIF-1 mediates reporter gene activity and endogenous HIF-1 target gene expression, including elevation of transcription, mRNA, and protein levels of the vascular endothelial growth factor (VEGF). Ciclopirox inhibits growth of C. albicans yeast and hyphal cells in a dose-dependent manner. Ciclopirox blocks H2O2-induced mitochondrial injury by maintaining mitochondrial transmembrane potential (Deltapsim). Ciclopirox completely blocks H2O2-stimulated release of lactate dehydrogenase (a marker of cell death) and decreases in MTT reduction (a marker of mitochondrial function) in adenocarcinoma SK-HEP-1 cells. Ciclopirox effectively inhibits H2O2-induced mitochondrial permeability transition pore (MPTP) opening. Ciclopirox increases the MTP, maintained it high, and blocks the ATP depletion in glucose-deprived SIN-1-treated astrocytes. Ciclopirox protects astrocytes from peroxynitritecytotoxicity by attenuating peroxynitrite-induced mitochondrial dysfunction. Ciclopirox is a substituted pyridone antimycotic drug, unrelated to the imidazole derivatives and its topical application ensures maximum local bioavailability. Ciclopirox acts on fungi by inhibiting the intracellular uptake of essential substrates and ions and this probably acts on the Candida ability to express its adherence mechanisms.