Abstract
The synthesis and antitumor activity of water-soluble amino acid prodrugs of amino-combretastatins were reported. Among the synthesized compounds, 7e (CS-39-L-Ser HCI, AC-7700) showed enhanced antitumor activity and decreased toxicity in a Colon 26 murine adenocarcinoma model. Compound 7e showed improved solubility and was easily formulated for in vivo administration. Compound 7e was cleaved to generate the parent compound, CS-39, in the whole blood of mice as well as man, possibly by the action of amino peptidase on the erythrocyte membrane.
MeSH terms
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Animals
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Antineoplastic Agents / chemical synthesis*
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Antineoplastic Agents / pharmacokinetics
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Antineoplastic Agents / pharmacology*
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Bibenzyls / chemical synthesis*
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Bibenzyls / pharmacokinetics
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Bibenzyls / pharmacology
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Colonic Neoplasms / drug therapy
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Drug Design
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Drug Stability
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Humans
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Hydrogen-Ion Concentration
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Hydrolysis
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Mice
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Mice, Inbred Strains
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Neoplasm Transplantation
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Prodrugs / chemical synthesis*
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Prodrugs / pharmacokinetics
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Prodrugs / pharmacology*
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Solubility
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Tumor Cells, Cultured
Substances
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Antineoplastic Agents
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Bibenzyls
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Prodrugs