Abstract
A series of novel spirolactone-type diterpenoid derivatives of oridonin (12a-j) were designed and synthesized. All the target compounds showed improved anti-proliferative activity against a panel of human cancer cell lines and the most effective compound 12j was more potent than positive control Taxol in K562 and Bel-7402 cells with IC(50) values of 0.39 μM and 1.39 μM, respectively. The cellular mechanisms showed that compound 12j induced apoptosis at low micromolar concentrations in human hepatoma Bel-7402 cells. These results demonstrate that the spirolactone-type diterpenoid derivatives of oridonin have optimized growth inhibitory activity against cancer cells and interesting apoptosis-inducing ability.
Copyright © 2012 Elsevier Masson SAS. All rights reserved.
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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Antineoplastic Agents / chemical synthesis*
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / pharmacology*
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Apoptosis / drug effects*
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Cell Cycle / drug effects
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Cell Line, Tumor
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Diterpenes / chemical synthesis
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Diterpenes / chemistry
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Diterpenes / pharmacology
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Diterpenes, Kaurane* / chemical synthesis
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Diterpenes, Kaurane* / chemistry
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Diterpenes, Kaurane* / pharmacology
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Flow Cytometry
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Humans
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Inhibitory Concentration 50
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Liver Neoplasms / drug therapy*
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Models, Molecular
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Paclitaxel / therapeutic use
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Spironolactone / chemical synthesis
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Spironolactone / chemistry
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Spironolactone / pharmacology
Substances
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Antineoplastic Agents
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Diterpenes
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Diterpenes, Kaurane
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oridonin
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Spironolactone
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kaurene
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Paclitaxel