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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antineoplastic Agents / chemical synthesis
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Antineoplastic Agents / pharmacology
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Diphosphates / chemistry
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Diphosphates / metabolism
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Humans
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MCF-7 Cells / drug effects
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Mice
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Neoplasms / drug therapy*
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Phosphorylation
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Prodrugs / chemical synthesis*
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Prodrugs / chemistry
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Prodrugs / pharmacokinetics*
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Quinolinium Compounds / chemical synthesis
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Quinolinium Compounds / pharmacology*
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Solubility
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Structure-Activity Relationship
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Xenograft Model Antitumor Assays
Substances
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Antineoplastic Agents
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Diphosphates
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Prodrugs
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Quinolinium Compounds