Abstract
A series of 4-anilinoquinoline derivatives related to the known inhibitor SGI-1027, containing side chains of varying pK(a), were prepared by acid-catalysed coupling of the pre-formed side chains with 4-chloroquinolines. The compounds were evaluated for their ability to reduce the level of DNMT1 protein in HCT116 human colon carcinoma cells by Western blotting. With a very strongly basic N-methylpyridinium side chain, only NHCO-linked compounds were effective, whereas less strongly basic ((diaminomethylene)hydrazono)ethyl or 3-methylpyrimidine-2,4-diamine side chains allowed both NHCO- and CONH-linked compounds to show activity. In contrast, the pK(a) of the quinoline unit had little apparent influence on activity.
Copyright © 2013 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Aniline Compounds / chemical synthesis*
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Aniline Compounds / chemistry
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Antineoplastic Agents / chemical synthesis*
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Antineoplastic Agents / chemistry
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DNA (Cytosine-5-)-Methyltransferase 1
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DNA (Cytosine-5-)-Methyltransferases / antagonists & inhibitors*
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DNA (Cytosine-5-)-Methyltransferases / chemistry
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DNA (Cytosine-5-)-Methyltransferases / genetics
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Gene Expression / drug effects
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HCT116 Cells
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Humans
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Neoplasm Proteins / antagonists & inhibitors*
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Neoplasm Proteins / chemistry
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Neoplasm Proteins / genetics
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Quinolines / chemical synthesis*
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Quinolines / chemistry
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Structure-Activity Relationship*
Substances
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Aniline Compounds
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Antineoplastic Agents
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Neoplasm Proteins
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Quinolines
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DNA (Cytosine-5-)-Methyltransferase 1
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DNA (Cytosine-5-)-Methyltransferases
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DNMT1 protein, human