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首页> 外文期刊>Applied Microbiology and Biotechnology >Metabolism of the ethanolamine-type antihistamine diphenhydramine (Benadryl)(TM) by the fungus Cunninghamella elegans
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Metabolism of the ethanolamine-type antihistamine diphenhydramine (Benadryl)(TM) by the fungus Cunninghamella elegans

机译：秀丽线虫Cunninghamella elegans对乙醇胺型抗组胺苯海拉明（Benadryl）（TM）的代谢

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Two strains of the filamentous fungus Cunninghamella elegans (ATCC 9245 and ATCC 36112) were grown in Sabouraud dextrose broth and screened for the ability to metabolize the ethanolamine-type antihistamine diphenhydramine. Based on the amount of parent drug recovered after 7 days incubation, both C, elegans strains metabolized approximately 74% of the diphenhydramine, 58% of this being identified as organic extractable metabolites. The organic extractable metabolites were isolated by reversed-phase high-performance liquid chromatography and identified by analyzing their mass and nuclear magnetic resonance spectra. Desorption chemical ionization mass spectrometry (DCIMS) with deuterated ammonia was used to differentiate possible isobaric diphenhydramine metabolites and to probe the mechanisms of ion formation under ammonia DCIMS conditions. C. elegans transformed diphenhydramine by demethylation, oxidation, and N-acetylation. The major metabolites observed were diphenhydramine-N-oxide (3%), N-desmethyldiphenhydramine (30%), N-acetyldidesmethyldiphenhydramine (13%), and N-acetyl-N-desmethyldiphenhydramine (12%). These compounds are known mammalian metabolites of diphenhydramine and may be useful for further toxicological studies. [References: 15]
机译：在Sabouraud葡萄糖肉汤中培养了两种线状真菌秀丽线虫Cunninghamella elegans（ATCC 9245和ATCC 36112），并筛选了代谢乙醇胺型抗组胺苯海拉明的能力。根据孵育7天后回收的母体药物的量，两种秀丽隐杆线虫菌株均代谢了约74％的苯海拉明，其中58％被鉴定为有机可提取代谢物。通过反相高效液相色谱法分离有机可提取代谢物，并通过分析其质量和核磁共振谱进行鉴定。具有氘化氨的解吸化学电离质谱（DCIMS）用于区分可能的同量异苯二酚苯海拉明代谢物，并探讨在氨DCIMS条件下离子形成的机理。秀丽隐杆线虫通过去甲基化，氧化和N-乙酰化转化苯海拉明。观察到的主要代谢物是苯海拉明-N-氧化物（3％），N-去甲基苯海拉明（30％），N-乙酰基二甲基苯海拉明（13％）和N-乙酰基-N-去甲基苯海拉明（12％）。这些化合物是苯海拉明的已知哺乳动物代谢产物，可用于进一步的毒理学研究。 [参考：15]

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