Abstract
Ten novel camptothecin (CPT) derivatives devoid of the lactone function in the E-ring were synthesized and evaluated as anticancer agents. Several of these CPT analogues bearing a five-membered E-ring are potent inhibitors of the DNA relaxation and cleavage reactions catalyzed by topoisomerase I and exhibit promising cytotoxic activities with IC(50) values in the nM range. This is the first successful design of lactone-free CPT, providing thus a new avenue to the development of topoisomerase I targeted antitumor agents.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antineoplastic Agents, Phytogenic / chemical synthesis*
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Antineoplastic Agents, Phytogenic / pharmacology
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Camptothecin / analogs & derivatives*
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Camptothecin / pharmacology
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Cell Division / drug effects
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Cell Line, Tumor / drug effects
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DNA / metabolism
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DNA Topoisomerases, Type I / metabolism
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Drug Design
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Drug Resistance
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Enzyme Inhibitors / chemical synthesis
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Enzyme Inhibitors / pharmacology
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Humans
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Lactones / chemistry
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Structure-Activity Relationship
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Topoisomerase I Inhibitors*
Substances
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Antineoplastic Agents, Phytogenic
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Enzyme Inhibitors
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Lactones
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Topoisomerase I Inhibitors
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DNA
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DNA Topoisomerases, Type I
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Camptothecin