Imazalil is an imidazole fungicide that inhibits ergosterol biosynthesis.1 Imazalil inhibits the growth of various fungi in vitro including P. italicum, A. niger, U. maydis, B. alii, and C. cucumerinum in a pH-dependent manner (MICs = 0.005-2 μg/ml at pH 7).2 It inhibits S. cerevisiae, but not rat liver microsomal, cytochrome P450 enzymes (CYPs; IC50s = 0.088 and 80 μM, respectively), as well as aromatase CYP19 from human placental microsomes (IC50 = 0.34 μM).1,3 Imazalil activates the murine pregnane X receptor (PXR) in a concentration-dependent manner in a cell-based reporter assay.4 It increases hepatic CYP3A11 and CYP2B10 mRNA levels in mice when administered at a dose of 100 mg/kg. Imazalil also increases Ki-67-positive nuclei in liver sections and hepatic MCM2 mRNA levels, markers of cell proliferation, in mice when co-administered with the murine constitutive androstane receptor (mCAR) agonist TCPOBOP . Formulations containing imazalil have been used to control fungal infection in agriculture.
1.Vanden Bossche, H., Lauwers, W., Willemsens, G., et al.Molecular basis for the antimycotic and antibacterial activity of N-substituted imidazoles and triazoles: The inhibition of isoprenoid biosynthesisPestic. Sci.15(2)188-198(1984) 2.Siegel, M.R., Kerkenaar, A., and Kaars Sijpesteijn, A.Antifungal activity of the systemic fungicide imazalilNeth. J. Pl. Path.83(Suppl. 1)121-133(1977) 3.Vinggaard, A.M., Hnida, C., Breinholt, V., et al.Screening of selected pesticides for inhibition of CYP19 aromatase activity in vitroToxicol. In Vitro14(3)227-234(2000) 4.Yoshimaru, S., Shizu, R., Tsuruta, S., et al.Acceleration of murine hepatocyte proliferation by imazalil through the activation of nuclear receptor PXRJ. Toxicol. Sci.43(7)443-450(2018)