Synthesis and cytotoxic activity of a glucuronylated prodrug of nornitrogen mustard.
A new glucuronylated prodrug of nornitrogen mustard, incorporating the same spacer group as the doxorubicin prodrug HMR 1826, has been prepared. Upon exposure to E. coli beta-glucuronidase, fast hydrolysis occurs but a lower cytotoxicity against LoVo cancer cells is observed compared to the nornitrogen mustard alone. This is explained by cyclization of the intermediate carbamic acid to the inactive chloroethyl oxazolidinone.
Papot
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Laboratoire de Synthèse et Réactivité des Substances naturelles, Université de Poitiers et CNRS, France.
Combaud
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Bosslet
K
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Gerken
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Czech
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J
Gesson
J P
JP
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D003110:Colonic Neoplasms; D003500:Cyclization; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D004926:Escherichia coli / Q000201:enzymology; D005965:Glucuronates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D005966:Glucuronidase / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D015394:Molecular Structure; D009588:Nitrogen Mustard Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D023303:Oxazolidinones / Q000737:chemistry; D011355:Prodrugs / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D005965:Glucuronates; D009588:Nitrogen Mustard Compounds; D023303:Oxazolidinones; D011355:Prodrugs; D005966:Glucuronidase; C004933:nornitrogen mustard