title: Synthesis and cytotoxic activity of a glucuronylated prodrug of nornitrogen mustard.
abstract: 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.
authors.affiliation: Laboratoire de Synthèse et Réactivité des Substances naturelles, Université de Poitiers et CNRS, France.
authors.forename: S
authors.initials: S
authors.lastname: Papot
authors.forename: D
authors.initials: D
authors.lastname: Combaud
authors.forename: K
authors.initials: K
authors.lastname: Bosslet
authors.forename: M
authors.initials: M
authors.lastname: Gerken
authors.forename: J
authors.initials: J
authors.lastname: Czech
authors.forename: J P
authors.initials: JP
authors.lastname: Gesson
mesh_terms: 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
chemical_list: D000970:Antineoplastic Agents; D005965:Glucuronates; D009588:Nitrogen Mustard Compounds; D023303:Oxazolidinones; D011355:Prodrugs; D005966:Glucuronidase; C004933:nornitrogen mustard