Abstract
A set of novel borrelidin analogues have been prepared by precursor-directed biosynthesis. Structure-activity relationship analysis suggests that steric structural arrangement within the C17 side chain is important for differentiating cytotoxic and anti-angiogenic activities. A C17-cyclobutyl analogue 3 was found to have markedly increased selectivity for in vitro angiogenesis inhibition over cytotoxicity and is therefore potentially useful as an anticancer agent.
MeSH terms
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Angiogenesis Inhibitors / chemical synthesis
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Angiogenesis Inhibitors / pharmacology*
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Antineoplastic Agents / chemical synthesis
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Antineoplastic Agents / pharmacology*
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Cell Line, Tumor / drug effects
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Cyclobutanes / chemistry*
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Fatty Alcohols / chemical synthesis
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Fatty Alcohols / pharmacology
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Humans
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Inhibitory Concentration 50
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Structure-Activity Relationship
Substances
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Angiogenesis Inhibitors
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Antineoplastic Agents
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Cyclobutanes
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Fatty Alcohols
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borrelidin