Bitertanol (Synonyms: Biloxazol)

Bitertanol is a broad-spectrum triazole fungicide that is active against a variety of fungi, including V. inaequalis and V. pirina, which are responsible for apple and pear scab, respectively, as well as S. mors-uvae and P. ribis, which are responsible for American gooseberry mildew and leaf spot in black currants, respectively.¹ It is active against isolates of V. inaequalis (MICs = 0.6 and 1 µg/ml) but repeated use leads to resistance and cross-resistance (MICs = 9.8-13 µg/ml for bitertanol-resistant isolates).² Bitertanol inhibits the cytochrome P450 (CYP450) isoform CYP3A4 (IC₅₀ = 2.74 µM) and inhibits androgenic activity induced by the androgen receptor agonist DHT in a yeast two-hybrid assay (IC₅₀ = 79.85 µM).³ In rats, bitertanol (10-300 mg/kg, i.p.) increases operant responding on one- and five-minute fixed interval schedules with no effect on motor activity.⁴

1.Birch, P.A., Rose, P.W., and Wainwright, A.A broad spectrum fungicide of the triazole group for use in pome and bush fruitBrit. Crop Prot. Conf. - Pests and Dis., Proc.11(2)545-554(1981) 2.Hildebrand, P.D., Lockhart, C.L., Newberry, R.J., et al.Resistance of Venturia inaequalis to bitertanol and other demethylation-inhibiting fungicidesCan. J. Plant Path.10(4)311-316(1988) 3.Lv, X., Pan, L., Wang, J., et al.Effects of triazole fungicides on androgenic disruption and CYP3A4 enzyme activityEnviron. Pollut.222(2016)504-512(2017) 4.Allen, A.R., and MacPhail, R.C.Bitertanol, a triazole fungicide, increases operant responding but not motor activityNeurotoxicol. Teratol.15(4)237-242(1993)