Abstract
The reaction of direct condensation between S-ethyl-N-(7-oxabicyclo-[2.2.1]heptane-2,3-dicarbonyl)isothiosemicarbazide (1) and primary amines was used for synthesizing new N-substituted amides of 3-(3-ethylthio-1,2,4-triazol-5-yl)-7-oxabicyclo-[2.2.1]heptane-2-carboxylic acid (2-12) as norcantharadin analogs. Moreover, the anticancer activity of the obtained compounds was studied. Among all compounds, the N-3-methylbutyl amide of 3-(3-ethylthio-1,2,4-triazol-5-yl)-7-oxabicyclo-[2.2.1]heptane-2-carboxylic acid (4) presented selective in vitro toxic and antiproliferative effects against the human hepatoma cell line Hep3B, without affecting normal human liver stellate cells (LX-2 cell line).
Keywords:
1,2,4-Triazole; Amides; Anticancer; Hep3B; Norcantharidin.
© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
MeSH terms
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Antineoplastic Agents / chemical synthesis*
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Antineoplastic Agents / pharmacology*
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Antineoplastic Agents / toxicity
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Bridged Bicyclo Compounds, Heterocyclic / chemical synthesis*
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Bridged Bicyclo Compounds, Heterocyclic / pharmacology*
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Bridged Bicyclo Compounds, Heterocyclic / toxicity
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Carcinoma, Hepatocellular / drug therapy*
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Carcinoma, Hepatocellular / pathology
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Cell Line, Tumor
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Cell Proliferation / drug effects
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Cell Survival / drug effects
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Dose-Response Relationship, Drug
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Drug Design
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Hepatic Stellate Cells / drug effects
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Hepatic Stellate Cells / pathology
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Humans
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Inhibitory Concentration 50
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Liver Neoplasms / drug therapy*
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Liver Neoplasms / pathology
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Molecular Structure
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Structure-Activity Relationship
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Time Factors
Substances
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Antineoplastic Agents
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Bridged Bicyclo Compounds, Heterocyclic
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norcantharidin