Abstract
Hybrids of vinca alkaloids and phomopsin A have been elaborated with the aim of interfering with the "vinca site" and the "peptide site" of the vinca domain in tubulin. They were synthesized by an efficient one-pot procedure that directly links the octahydrophomopsin lateral chain to the velbenamine moiety of 7'-homo-anhydrovinblastine. In their modeled complexes with tubulin, these hybrids were found to superimpose nicely on the tubulin-bound structures of vinblastine and phomopsin A. This good matching can account for the fact that two of them are very potent inhibitors of microtubules assembly and are cytotoxic against four cancer cell lines.
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 / pharmacology
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Cell Line, Tumor
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Drug Screening Assays, Antitumor
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Humans
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Models, Molecular
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Mycotoxins / chemical synthesis*
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Mycotoxins / chemistry
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Mycotoxins / pharmacology
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Tubulin / chemistry
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Tubulin Modulators / chemical synthesis
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Tubulin Modulators / chemistry
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Tubulin Modulators / pharmacology
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Vinblastine / analogs & derivatives*
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Vinblastine / chemical synthesis*
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Vinblastine / chemistry
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Vinblastine / pharmacology
Substances
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Antineoplastic Agents
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Mycotoxins
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Tubulin
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Tubulin Modulators
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Vinblastine
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phomopsin