Abstract
A severe limitation in cancer therapy is the often insufficient differentiation between malign and benign tissue using known chemotherapeutics. One approach to decrease side effects is antibody-directed enzyme prodrug therapy (ADEPT). We have developed new glycosidic prodrugs such as (-)-(1S)-26 b based on the antibiotic (+)-duocarmycin SA ((+)-1) with a QIC(50) value of 3500 (QIC(50)=IC(50) of prodrug/IC(50) of prodrug+enzyme) and an IC(50) value for the corresponding drug (prodrug+enzyme) of 16 pM. The asymmetric synthesis of the precursor (-)-(1S)-19 was performed by arylation of the enantiomerically pure epoxide (+)-(S)-29 (> or = 98 % ee).
Publication types
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Research Support, Non-U.S. Gov't
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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Duocarmycins
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Glycosides / chemical synthesis*
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Glycosides / chemistry
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Glycosides / pharmacology*
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Humans
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Indoles / chemical synthesis
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Indoles / chemistry
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Indoles / pharmacology
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Inhibitory Concentration 50
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Neoplasms / drug therapy
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Prodrugs / chemical synthesis*
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Prodrugs / chemistry
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Prodrugs / pharmacology*
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Pyrroles / chemical synthesis
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Pyrroles / chemistry
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Pyrroles / pharmacology
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Stereoisomerism
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beta-Galactosidase / metabolism
Substances
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Antineoplastic Agents
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Duocarmycins
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Glycosides
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Indoles
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Prodrugs
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Pyrroles
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duocarmycin SA
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beta-Galactosidase