Source:http://linkedlifedata.com/resource/pubmed/id/17265417
Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
3
|
| pubmed:dateCreated |
2007-4-9
|
| pubmed:abstractText |
Naphthoquinone derivatives are under investigation as potential therapeutic agents. Some such compounds are known, however, to be toxic to both animals and humans. Many naphthoquinone derivatives are haemolytic agents, while others cause necrosis of tubular epithelial cells. In the present study, the short-term toxicity of 16 derivatives of 1,2- and 1,4-naphthoquinone has been examined in rats in order to give information on structure-activity relationships. All the naphthoquinones except one caused haemolytic anaemia, but only hydroxy and amino derivatives were nephrotoxic. Among derivatives of 2-amino-1,4-naphthoquinone, substitution in the 3-position decreased haemolytic activity and abolished nephrotoxicity. Methylation of the hydroxyl group of 2-hydroxy-1,4-naphthoquinone had a similar effect. In contrast, methylation of the amino group of 2-amino-1,4-naphthoquinone increased the severity of both haemolysis and renal damage. Among the 1,2-naphthoquinones tested, the 4-methoxy and 4-amino derivatives were more toxic than the corresponding 1,4-isomers, although 4-methyl-1,2-naphthoquinone was less toxic than 2-methyl-1,4-naphthoquinone. At present, the toxicity of naphthoquinone derivatives cannot accurately be predicted on the basis of their chemical structure. In developing naphthoquinone derivatives for use in humans, toxicological studies in animals should be conducted at an early stage, bearing in mind that clinical studies have shown that humans appear to be particularly vulnerable to the nephrotoxic action of these compounds, and that certain individuals are unusually susceptible to their haemolytic action.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/1,2-naphthoquinone,
http://linkedlifedata.com/resource/pubmed/chemical/1,4-naphthoquinone,
http://linkedlifedata.com/resource/pubmed/chemical/Creatinine,
http://linkedlifedata.com/resource/pubmed/chemical/Hemolytic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/NAD(P)H Dehydrogenase (Quinone),
http://linkedlifedata.com/resource/pubmed/chemical/NQO1 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Naphthoquinones,
http://linkedlifedata.com/resource/pubmed/chemical/Urea,
http://linkedlifedata.com/resource/pubmed/chemical/lawsone
|
| pubmed:status |
MEDLINE
|
| pubmed:issn |
0260-437X
|
| pubmed:author | |
| pubmed:copyrightInfo |
(c) 2007 John Wiley & Sons, Ltd.
|
| pubmed:issnType |
Print
|
| pubmed:volume |
27
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
262-9
|
| pubmed:dateRevised |
2007-11-15
|
| pubmed:meshHeading |
pubmed-meshheading:17265417-Anemia, Hemolytic,
pubmed-meshheading:17265417-Animals,
pubmed-meshheading:17265417-Catalysis,
pubmed-meshheading:17265417-Creatinine,
pubmed-meshheading:17265417-Dose-Response Relationship, Drug,
pubmed-meshheading:17265417-Female,
pubmed-meshheading:17265417-Hemolytic Agents,
pubmed-meshheading:17265417-Kidney,
pubmed-meshheading:17265417-Kidney Diseases,
pubmed-meshheading:17265417-Molecular Structure,
pubmed-meshheading:17265417-NAD(P)H Dehydrogenase (Quinone),
pubmed-meshheading:17265417-Naphthoquinones,
pubmed-meshheading:17265417-Organ Size,
pubmed-meshheading:17265417-Rats,
pubmed-meshheading:17265417-Rats, Sprague-Dawley,
pubmed-meshheading:17265417-Spleen,
pubmed-meshheading:17265417-Stereoisomerism,
pubmed-meshheading:17265417-Structure-Activity Relationship,
pubmed-meshheading:17265417-Urea
|
| pubmed:articleTitle |
Structure-activity relationships in the haemolytic activity and nephrotoxicity of derivatives of 1,2- and 1,4-naphthoquinone.
|
| pubmed:affiliation |
AgResearch, Ruakura Agricultural Research Centre, Private Bag 3123, Hamilton, New Zealand. rex.munday@agresearch.co.nz
|
| pubmed:publicationType |
Journal Article
|