Zhu Yong-Zhe, Keum Young Soo, Yang Lin, Lee Hyeri, Park Heewon, Kim Jeong-Han
College of Chemistry and Pharmacy, Qingdao Agricultural University, Changcheng Road, Chengyang, Qingdao City, Shandong Province 266-109, China.
J Agric Food Chem. 2010 Dec 8;58(23):12379-84. doi: 10.1021/jf102980y. Epub 2010 Nov 3.
Mepanipyrim is a fungicide against several plant pathogens. However, no metabolic details have been established in fungi, which is the most important biomass in the natural environment. Cunninghamella elegans is a well-known fungal species with its strong resemblance to the mammalian xenobiotic metabolism. In this study, the detailed metabolic pathways of mepanipyrim were investigated with C. elegans. Approximately 87% of mepanipyrim was removed within 12 h with concomitant accumulation of nine metabolites. Structures of the metabolites were fully or tentatively identified with GC-MS and (1)H NMR. To determine the possible role of representative oxidative enzymes, piperonyl butoxide and methimazole were treated, and the kinetic responses of mepanipyrim and its metabolites were measured. Dose-dependent inhibition of metabolism was observed with piperonyl butoxide, while methimazole also inhibited the metabolism less effectively. The results indicate the possible involvement of cytochrome P450 and flavin-dependent monooxygenase in mepanipyrim metabolism. Comprehensive metabolic pathways can be deduced from the detailed analysis of metabolite profiles in control and inhibitor assays.
甲嘧磺隆是一种针对多种植物病原体的杀菌剂。然而，在真菌（自然环境中最重要的生物量）中尚未确定其代谢细节。雅致小克银汉霉是一种著名的真菌物种，与哺乳动物的异生物质代谢有很强的相似性。在本研究中，利用雅致小克银汉霉研究了甲嘧磺隆的详细代谢途径。在12小时内约87%的甲嘧磺隆被去除，同时积累了9种代谢产物。通过气相色谱 - 质谱联用仪（GC-MS）和氢核磁共振波谱（¹H NMR）对代谢产物的结构进行了完全或初步鉴定。为了确定代表性氧化酶的可能作用，使用了胡椒基丁醚和甲巯咪唑进行处理，并测量了甲嘧磺隆及其代谢产物的动力学响应。观察到胡椒基丁醚对代谢有剂量依赖性抑制作用，而甲巯咪唑对代谢的抑制作用也较弱。结果表明细胞色素P450和黄素依赖性单加氧酶可能参与了甲嘧磺隆的代谢。通过对对照和抑制剂试验中代谢产物谱的详细分析，可以推断出全面的代谢途径。
