Abstract
Inhibitors of kinesin spindle protein (KSP) are a promising class of anticancer agents that cause mitotic arrest in cells from a failure to form functional bipolar mitotic spindles. Here, we report the synthesis and biological evaluation of a novel series of tetrahydro-beta-carboline analogs based on the structure of the known KSP inhibitor HR22C16. Preferred compounds 11b, 12a and 19b were identified as potent inhibitors in a KSP ATPase assay with good anti-proliferative activity in A549 cells.
Copyright 2010 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antineoplastic Agents / chemistry*
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Antineoplastic Agents / pharmacology
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Carbolines / chemical synthesis
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Carbolines / chemistry*
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Carbolines / pharmacology
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Cell Line, Tumor
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Drug Discovery
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Drug Screening Assays, Antitumor
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Enzyme Inhibitors / chemistry*
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Enzyme Inhibitors / pharmacology
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Humans
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Indoles / chemistry
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Indoles / pharmacology
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Kinesins / antagonists & inhibitors*
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Kinesins / metabolism
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Phenols / chemistry
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Phenols / pharmacology
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Spindle Apparatus / enzymology*
Substances
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1-(3-hydroxyphenyl)-2-(4-aminobenzoyl)-6-chloro-1,2,3,4-tetrahydro-beta-carboline
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1-(3-hydroxyphenyl)-2-(beta-aminopropionyl)-8-chloro-1,2,3,4-tetrahydro-beta-carboline
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6-methyl-1-(indol-3-yl)-2-butyryl-1,2,3,4-tetrahydro-beta-carboline
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Antineoplastic Agents
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Carbolines
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Enzyme Inhibitors
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HR22C16
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Indoles
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Phenols
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Kinesins