Abstract
A new class of human GST inhibitors has been identified via rational design approach; we report their discovery, synthesis, inhibitory activity, and synergetic effect in combination with cisplatin against A549 lung cancer cell line. The results of this effort show that the lead 4-O-decyl-gabosine D (24) has optimum synergetic effect in A549 human lung adenocarcinoma epithelial cell and that this activity involves inhibition of glutathione S-transferase M1, apparently consistent with siRNA-mediated knockdown of GSTM1 gene.
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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Cell Survival / drug effects
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Cisplatin / pharmacology*
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Cyclohexanones / chemical synthesis
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Cyclohexanones / chemistry
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Cyclohexanones / pharmacology*
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Drug Resistance, Neoplasm / drug effects*
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Drug Screening Assays, Antitumor
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Drug Synergism
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Glutathione Transferase / antagonists & inhibitors*
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Glutathione Transferase / genetics
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Humans
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Isoenzymes / antagonists & inhibitors
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Lung Neoplasms
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RNA, Small Interfering / genetics
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Structure-Activity Relationship
Substances
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4-O-decyl-gabosine D
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Antineoplastic Agents
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Cyclohexanones
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Isoenzymes
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RNA, Small Interfering
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gabosine D
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Glutathione Transferase
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glutathione S-transferase M1
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Cisplatin