Abstract
Two new glucuronide paclitaxel prodrugs have been synthesized. Linked to the 2'-OH of the drug by a carbonate function, they include a self-immolative spacer bearing an arylnitro or arylamino group between the drug and the glucuronic acid residue. Both prodrugs were well detoxified and easily cleaved in the presence of beta-D-glucuronidase with fast removal of the spacer, releasing paclitaxel. The arylamino spacer-containing prodrug, more stable than the corresponding nitro analogue, was selected for further studies.
MeSH terms
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Antineoplastic Agents / chemical synthesis*
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / pharmacology*
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Cell Line, Tumor
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Drug Design
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Drug Screening Assays, Antitumor
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Escherichia coli / enzymology
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Glucuronidase / metabolism
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Humans
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Inactivation, Metabolic
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Paclitaxel / analogs & derivatives*
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Paclitaxel / chemical synthesis
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Paclitaxel / chemistry
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Paclitaxel / pharmacology
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Prodrugs / chemical synthesis*
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Prodrugs / chemistry
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Prodrugs / pharmacokinetics
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Prodrugs / pharmacology*
Substances
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Antineoplastic Agents
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Prodrugs
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Glucuronidase
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Paclitaxel