期刊
ENDOCRINE RESEARCH
卷 30, 期 3, 页码 387-394出版社
TAYLOR & FRANCIS INC
DOI: 10.1081/ERC-200035093
关键词
azoles; antifungals; pesticides; CYP19; aromatase; monooxygenase; steroid metabolism; estrogen biosynthesis; endocrine disruption; enzyme inhibition
Azoles (imidazoles and triazoles) are used as antifungal agents in agriculture and in medicine, and also for antiestrogen therapy, e.g., for breast cancer treatment. Antifungal activity is based on inhibition of fungal CYP51 (lanosterol 14alpha-demethylase), and estrogen biosynthesis reduction is due to azole inhibition of CYP19 (aromatase). Inhibition of aromatase by antifungal agents is usually an unwanted side effect and may cause endocrine disruption. A fluorimetric assay based on human recombinant CYP19 enzyme with dibenzylfluorescein as a substrate was used to compare the inhibitory potency of 22 azole compounds. Dose responses were established and duplicate datasets were analyzed with a nonlinear mixed-effects model with cumulative normal distribution for the logarithm of concentration. IC50 values (50% inhibitory concentration) of 13 fungicides used in agriculture ranged more than 700-fold, starting from 0.047 muM. The potency of seven human drugs.
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