title: Identification, synthesis, and safety assessment of forchlorfenuron (1-(2-chloro-4-pyridyl)-3-phenylurea) and its metabolites in kiwifruits.
abstract: Identification and evaluation of safety of forchlorfenuron ((1-(2-chloro-4-pyridyl)-3-phenylurea)), 1, metabolites after biotransformation in kiwifruit is the objective of this study. To elucidate properties of these metabolites, liquid chromatography hybrid ion trap time-of-flight mass spectrometry (LC-IT-TOF-MS) was applied, with MetID Solution and Formula Predictor Software in positive mode. Cytotoxicity of forchlorfenuron and its metabolites were tested through sulforhodamine B assays against normal Chinese hamster ovary cells (CHO). As deduced from characteristic fragment ions of forchlorfenuron, then confirmed by comparison with synthetic standards, as well as characterized by NMR and mass spectrometry techniques, results indicate the presence of 4-hydroxyphenyl-forchlorfenuron, 2, 3-hydroxyphenyl-forchlorfenuron, 3, and forchlorfenuron-4-O-β-D-glucoside, 5. Forchlorfenuron (IC50 = 12.12 ± 2.14 μM) and 4-hydroxyphenyl-forchlorfenuron (IC50 = 36.15 ± 1.59 μM), exhibits significant cytotoxicity against CHO, while 3-hydroxyphenyl-forchlorfenuron and forchlorfenuron-4-O-β-D-glucoside show no cytotoxicity.
authors.affiliation: ‡College of Food Science and Engineering, Qingdao Agricultural University, Chengyang 266109, Qingdao China.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Zhang
authors.forename: Kangquan
authors.initials: K
authors.lastname: Guo
authors.forename: Yubin
authors.initials: Y
authors.lastname: Bai
authors.affiliation: ⊥Beijing Office, Shimadzu International Trading (Shanghai), 14/F Life Tower, 16 Chaoyang Men Wai Street, Beijing 100020, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Dong
authors.forename: Zhenhong
authors.initials: Z
authors.lastname: Gao
authors.forename: Yahong
authors.initials: Y
authors.lastname: Yuan
authors.forename: Yuan
authors.initials: Y
authors.lastname: Wang
authors.forename: Laping
authors.initials: L
authors.lastname: Liu
authors.forename: Tianli
authors.initials: T
authors.lastname: Yue
mesh_terms: D029042:Actinidia / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D016466:CHO Cells; D002470:Cell Survival / Q000187:drug effects; D006224:Cricetinae; D003412:Cricetulus; D005638:Fruit / Q000737:chemistry / Q000378:metabolism; D013058:Mass Spectrometry; D010671:Phenylurea Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D010937:Plant Growth Regulators / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology
chemical_list: D010671:Phenylurea Compounds; D010937:Plant Growth Regulators; D011725:Pyridines; C116093:N-(2-chloro-4-pyridyl)-N'-phenylurea
keywords: LC-IT-TOF-MS; forchlorfenuron; metabolites; safety assessment