title: Mechanistic studies on regioselective dephosphorylation of phosphate prodrugs during a facile synthesis of antitumor phosphorylated 2-phenyl-6,7-methylenedioxy-1H-quinolin-4-one.
abstract: Phosphorylation of 2-(3-hydroxy-5-methoxyphenyl)-6,7-methylenedioxy-1H-quinolin-4-one (1) afforded diphosphate 2. We found that, upon treatment with methanol under mild conditions, 2 can undergo facile and highly regioselective dephosphorylation to give the monophosphate 3, with a phosphate group remaining on the phenyl ring. The details of the dephosphorylation process were postulated and then probed by LC-MS and HPLC analyses. Furthermore, as a preliminary study, the water soluble monophosphate prodrug 4 was tested for antitumor activity against a MCF-7 xenograft nude mice model.
authors.affiliation: Graduate Institute of Pharmaceutical Chemistry, China Medical University, No.91 Hsueh-Shih Road, Taichung, 40402, Taiwan.
authors.forename: Yung-Yi
authors.initials: YY
authors.lastname: Cheng
authors.forename: Chin-Yu
authors.initials: CY
authors.lastname: Liu
authors.forename: Li-Jiau
authors.initials: LJ
authors.lastname: Huang
authors.forename: Chi-Hung
authors.initials: CH
authors.lastname: Huang
authors.forename: Kuo-Hsiung
authors.initials: KH
authors.lastname: Lee
authors.forename: Cheng-Tung
authors.initials: CT
authors.lastname: Lin
authors.forename: Sheng-Chu
authors.initials: SC
authors.lastname: Kuo
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology; D011756:Diphosphates / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D061986:MCF-7 Cells / Q000187:drug effects; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy*; D010766:Phosphorylation; D011355:Prodrugs / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics*; D011806:Quinolinium Compounds / Q000138:chemical synthesis / Q000494:pharmacology*; D012995:Solubility; D013329:Structure-Activity Relationship; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D011756:Diphosphates; D011355:Prodrugs; D011806:Quinolinium Compounds