Ciclopirox ethanolamineS3019

Ciclopirox significantly inhibits the growth of C. albicans strain SC5314 cells, with MIC₈₀s of 1.0-2.0 μg/mL, growth decreased dramatically at the concentrations of >0.6 μg/mL, and almost complete growth inhibition at concentration of 0.7 μg/mL, unlike fluconazole which shows a much wider range of concentrations with intermediate inhibition. Like iron chelator bipyridine, Ciclopirox reduces cell growth by binding to iron ions, which can be reversed by addition of FeCl₃. Moreover, Ciclopirox treatment at subinhibitory concentration (0.6 μg/mL) only moderately reduces the virulence genes such as genes encoding secreted proteinases or lipases, but leads to a distinct up- or down-regulation of genes encoding iron permeases or transporters (FTR1, FTR2, and FTH1), a copper permease (CCC2), an iron reductase (CFL1), and a siderophore transporter (SIT1). Although the Candida drug resistance genes CDR1 and CDR2 are up-regulated after Ciclopirox treatment, no change in resistance or increased tolerance could be observed even after an incubation period of 6 months, in contrast to fluconazole in which the MICs for cells noticeably increase after 2 months. ^[1] Ciclopirox inhibits the growth of Aspergillus fumigatus strain B5233 with IC50 of 4.22 μM, more potently compared with deferiprone with IC50 of 1.29 mM. ^[2]