Abstract
The mitotic kinesin Eg5 (or KSP) is a crucial player in the development and function of the mitotic spindle. Inhibition of this protein leads to cell cycle arrest and apoptosis without interfering with other microtubule-dependent processes. Therefore, it is a potential target in cancer therapy. Here, we report the synthesis and biological evaluation of a small library of molecules based on the structure of the known Eg5 inhibitor HR22C16. One of these derivatives (compound trans-24) proved to be a potent and specific Eg5 inhibitor.
MeSH terms
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Animals
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Carbolines / chemical synthesis*
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Carbolines / chemistry
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Carbolines / pharmacology*
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Drug Screening Assays, Antitumor
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HeLa Cells
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Humans
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Indoles / chemistry
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Inhibitory Concentration 50
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Kinesins / antagonists & inhibitors*
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Kinesins / genetics
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Mitosis / drug effects*
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Molecular Structure
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Neurotoxins / chemical synthesis
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Neurotoxins / pharmacology
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Phenols / chemistry
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Xenopus Proteins / antagonists & inhibitors*
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Xenopus Proteins / genetics
Substances
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Carbolines
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HR22C16
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Indoles
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KIF11 protein, Xenopus
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Neurotoxins
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Phenols
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Xenopus Proteins
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tryptoline
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Kinesins