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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
2004-6-18
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pubmed:abstractText |
A number of 2-arylidenecyclohexanones (1a-h) were converted into the corresponding Mannich bases (2a-h) and (3a,f). Evaluation against murine L1210 cells as well as human Molt 4/C8 and CEM T-lymphocytes revealed the marked cytotoxicity of the Mannich bases and also the fact that almost invariably these compounds were more potent than the precursor enones (1a-h). Further evaluation of most of the Mannich bases towards a panel of nearly 60 human tumour cell lines confirmed their utility as potent cytotoxins. In this assay, the compounds showed growth-inhibiting properties greater than the anticancer alkylator melphalan. QSAR studies revealed that in some cell lines compounds possessing small electron-attracting aryl substituents showed the greatest potencies. Molecular modeling and X-ray crystallography demonstrated that various interatomic distances and torsion angles correlated with cytotoxicity. A representative compound (2a) demonstrated weak inhibiting properties towards human N-myristoyltransferase and stimulated a tyrosine protein kinase. A single dose of 100 mg/kg of most of the compounds did not prove to be lethal in mice.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
1475-6366
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pubmed:author |
pubmed-author:BalzariniJJ,
pubmed-author:ChamankhahMM,
pubmed-author:DanRR,
pubmed-author:De ClercqEE,
pubmed-author:DimmockJ RJR,
pubmed-author:NienaberK HKH,
pubmed-author:QuailJ WJW,
pubmed-author:SelvakumarPP,
pubmed-author:SharmaR KRK,
pubmed-author:StablesJ PJP,
pubmed-author:YangJJ,
pubmed-author:ZelloG AGA
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pubmed:issnType |
Print
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pubmed:volume |
19
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1-10
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:15202487-Acyltransferases,
pubmed-meshheading:15202487-Animals,
pubmed-meshheading:15202487-Antineoplastic Agents,
pubmed-meshheading:15202487-Crystallography, X-Ray,
pubmed-meshheading:15202487-Cyclohexanones,
pubmed-meshheading:15202487-Drug Screening Assays, Antitumor,
pubmed-meshheading:15202487-Humans,
pubmed-meshheading:15202487-Inhibitory Concentration 50,
pubmed-meshheading:15202487-Mannich Bases,
pubmed-meshheading:15202487-Mice,
pubmed-meshheading:15202487-Molecular Structure,
pubmed-meshheading:15202487-Protein-Tyrosine Kinases,
pubmed-meshheading:15202487-Quantitative Structure-Activity Relationship,
pubmed-meshheading:15202487-T-Lymphocytes,
pubmed-meshheading:15202487-Tumor Cells, Cultured
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pubmed:year |
2004
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pubmed:articleTitle |
Cytotoxic and topographical properties of 6-arylidene-2-dimethylaminomethylcyclohexanone hydrochlorides and related compounds.
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pubmed:affiliation |
College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, Saskatchewan S7N 5C9, Canada. dimmock@skyway.usask.ca
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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