Abstract
The introduction of a methylenthiol group at position 7 of camptothecin was carried out in four steps. This preparation also yielded the corresponding disulfide, which behaves as a prodrug due to its reactivity with glutathione. Assessment of their antiproliferative activities, investigations of their mechanism of action, and molecular modeling analysis indicated that the 7-modified camptothecin derivatives described herein maintain the biological activity and drug-target interactions of the parent compound.
Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antineoplastic Agents, Phytogenic / chemical synthesis
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Antineoplastic Agents, Phytogenic / chemistry*
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Antineoplastic Agents, Phytogenic / metabolism
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Antineoplastic Agents, Phytogenic / pharmacology*
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Camptothecin / analogs & derivatives*
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Camptothecin / chemical synthesis
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Camptothecin / metabolism
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Camptothecin / pharmacology*
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Cell Line, Tumor
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Cell Proliferation / drug effects
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Cell Survival / drug effects
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DNA Topoisomerases / metabolism
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Glutathione / metabolism
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Humans
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Models, Molecular
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Neoplasms / drug therapy
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Neoplasms / enzymology
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Prodrugs / chemical synthesis
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Prodrugs / chemistry*
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Prodrugs / metabolism
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Prodrugs / pharmacology*
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Topoisomerase I Inhibitors / chemical synthesis
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Topoisomerase I Inhibitors / chemistry
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Topoisomerase I Inhibitors / metabolism
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Topoisomerase I Inhibitors / pharmacology
Substances
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Antineoplastic Agents, Phytogenic
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Prodrugs
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Topoisomerase I Inhibitors
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DNA Topoisomerases
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Glutathione
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Camptothecin