Characterization of an epoxide‐derived metabolite of dictamnine using high‐performance liquid chromatography with hybrid linear trap quadrupole orbitrap mass spectrometry |
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| Authors: | Pinning Feng Xinrong Hu Xiaoliang Wu Jun Dong Xiuyu Cai |
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| Affiliation: | 1. Department of Laboratory Medicine, The First Affiliated Hospital of Sun Yat‐sen University, Guangzhou, P. R. China;2. Department of oncology, Nanxi Mountain hospital, Guilin, P. R. China;3. State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, P. R. China;4. Department of General Internal Medicine, Sun Yat‐Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, P. R. China |
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| Abstract: | Dictamnine (4‐methoxyfuro[2,3‐b]quinolone), a furoquinoline alkaloid of the Rutaceae plant family, has been reported to be a phototoxic and photomutagenic compound, whose exposure can cause carcinogenicity, cytotoxicity, and genotoxicity. Metabolic activation is suggested to play an important role in dictamnine‐induced toxicities, and the epoxide metabolite of dictamnine has been reported to be the main intermediate in vitro. The objective of this study was to identify N‐acetylcysteine conjugate(s) derived from this reactive dictamnine metabolite in vitro and in vivo. An N‐acetylcysteine conjugate of dictamnine was detected in microsomal incubations of dictamnine, as well as bile and urine samples of rats treated with dictamnine. The data obtained from the present work will facilitate the understanding of the mechanism behind dictamnine‐induced toxicities. |
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| Keywords: | N‐acetylcysteine conjugates Dictamnine Metabolic activation Reactive metabolites Toxicity |
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