Abstract
A dynamic combinatorial library of thiocolchicine-podophyllotoxin derivatives based on the disulfide bond exchange reaction is described. The influence of a biological target on the composition of the reaction mixture has been demonstrated. Use of high-resolution ESI mass spectrometry to evaluate the composition of the mixture shows promise for the design of new large libraries. The biological evaluation demonstrates that formation of a divalent compound affords a new chemical entity whose biological activity is not merely the sum of the single ligands activities, thus reflecting a different interaction with the biological target.
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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Cell Line, Tumor
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Cell Proliferation / drug effects
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Chromatography, High Pressure Liquid / methods
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Colchicine / analogs & derivatives*
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Colchicine / chemistry
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Colchicine / pharmacology
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Combinatorial Chemistry Techniques / methods*
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Disulfides / chemistry*
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Disulfides / pharmacology
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Drug Screening Assays, Antitumor
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Humans
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In Vitro Techniques
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Molecular Conformation
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Podophyllotoxin / chemistry*
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Podophyllotoxin / pharmacology
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Sensitivity and Specificity
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Spectrometry, Mass, Electrospray Ionization / methods
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Stereoisomerism
Substances
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Disulfides
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thiocholchicine
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Podophyllotoxin
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Colchicine