Abstract
Novel betulin derivatives were prepared and tested for their antitumor activity. Starting from 3-O-acetyl- or 3-O-methyl-betulinic aldehyde, the synthesis of C-28 ethynyl derivatives was performed; their subsequent transformation with several 1,3-dipolarophiles afforded pyrazoles and 1,2,3-triazoles. Their screening for antitumor activity was performed in a panel of 15 human cancer cell lines by a colorimetric SRB-assay. Thereby, several compounds revealed a higher cytotoxicity than betulinic acid. In addition, the encapsulation of the lead structure 7 into liposomes was investigated. The results from a dye exclusion test and from DNA laddering experiments provided evidence for an apoptotic cell death.
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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Betulinic Acid
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Cell Line, Tumor
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Colorimetry / methods
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Drug Screening Assays, Antitumor
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Fluorescent Dyes / chemistry
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Humans
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Liposomes
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Neoplasms / drug therapy*
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Neoplasms / pathology
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Pentacyclic Triterpenes
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Pyrazoles / chemical synthesis
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Pyrazoles / chemistry
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Pyrazoles / pharmacology
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Rhodamines / chemistry
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Structure-Activity Relationship
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Triazoles / chemical synthesis
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Triazoles / chemistry
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Triazoles / pharmacology
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Triterpenes / chemical synthesis
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Triterpenes / chemistry
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Triterpenes / pharmacology*
Substances
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Antineoplastic Agents
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Fluorescent Dyes
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Liposomes
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Pentacyclic Triterpenes
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Pyrazoles
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Rhodamines
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Triazoles
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Triterpenes
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lissamine rhodamine B
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betulin
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Betulinic Acid