Abstract
Homocamptothecin (hCPT) is a camptothecin (CPT) derivative with a seven-membered β-hydroxylactone E ring, which shows higher lactone stability and improves topoisomerase I (Topo I) inhibition activity. In an attempt to improve the antitumor activity of homocamptothecins, a series of 7-alkenyl-homocamptothecin derivatives was designed and synthesized based on a semisynthetic route starting from CPT. Most of the synthesized compounds exhibit higher cytotoxic activities on the A-549 tumor cell line than topotecan (TPT). Some compounds such as 2a and 2o show a broad in vitro antitumor spectrum and exhibit superior Topo I-inhibition activity.
Copyright © 2012 Verlag Helvetica Chimica Acta AG, Zürich.
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 / toxicity
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Apoptosis / drug effects
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Camptothecin / analogs & derivatives*
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Camptothecin / chemical synthesis
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Camptothecin / chemistry
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Camptothecin / toxicity
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Cell Line, Tumor
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DNA / metabolism
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DNA Cleavage
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DNA Topoisomerases, Type I / chemistry*
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DNA Topoisomerases, Type I / metabolism
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Humans
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Topoisomerase I Inhibitors / chemical synthesis*
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Topoisomerase I Inhibitors / chemistry
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Topoisomerase I Inhibitors / toxicity
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Topotecan / toxicity
Substances
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Antineoplastic Agents
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Topoisomerase I Inhibitors
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Topotecan
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DNA
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homocamptothecin
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DNA Topoisomerases, Type I
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Camptothecin