Abstract
The synthesis, the enantiomeric separation, and the characterization of new simple spiroketal derivatives have been performed. The synthesized compounds have shown a very high anticancer activity. Cell proliferation assay showed that they induce a remarkable inhibition of cell proliferation in all cell lines treated, depending on culture time and concentration. The compounds have also shown a potent nanomolar human telomerase inhibition activity and apoptosis induction. CD melting experiments demonstrate that spiroketal does not affect the G-quadruplex (G4) thermal stability. Docking studies showed that telomerase inhibition could be determined by a spiroketal interaction with the telomerase enzyme.
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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Apoptosis / drug effects
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Cell Line, Tumor
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Enzyme Inhibitors / chemical synthesis
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Enzyme Inhibitors / chemistry*
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Enzyme Inhibitors / pharmacology*
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Furans / chemical synthesis
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Furans / chemistry*
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Furans / pharmacology*
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G-Quadruplexes / drug effects
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Humans
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Models, Molecular
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Molecular Docking Simulation
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Neoplasms / drug therapy
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Neoplasms / metabolism
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Spiro Compounds / chemical synthesis
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Spiro Compounds / chemistry*
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Spiro Compounds / pharmacology*
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Stereoisomerism
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Structure-Activity Relationship
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Telomerase / antagonists & inhibitors*
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Telomerase / metabolism
Substances
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Antineoplastic Agents
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Enzyme Inhibitors
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Furans
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Spiro Compounds
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spiroketal
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Telomerase