Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
1-2
|
| pubmed:dateCreated |
1998-2-19
|
| pubmed:abstractText |
In recent years there has been a growing interest in the therapeutic application of L-ascorbic acid (AA) and its derivatives as anticancer agents. AA is a gamma-crotonolactone derivative with reactive hydroxyl groups at the 2- and 3-positions and an ethylene glycol substitution at the 4-position. Despite the various reports on AA toxicity, no work has been reported underlying the critical chemical structural features for its activity. The present study addresses this question. We tested in vivo, using malignant leukemia cell line P388D1, (i) L-AA and its isomers, (ii) substitution at the 2-position: -PO4, -SO4, O-Me, O-octadecyl, (iii) substitution at the 6-position: -PO4, -SO4, -palmitate, -stearate, (iv) substitution at the 2,6-position: dipalmitate, (v) 6-deoxy derivative: -Cl, -Br, -NH2 and (vi) dihydroxy gamma-crotonolactone with substitutions at the 4-position: -H, -CH3, -CH2-CH3 and -CH=CH2. L-AA and its isomers were very cytotoxic even at very low concentration. All 6-substituted and 6-deoxy derivatives were as toxic as AA. However, 2-substituted and 2,6-disubstituted AA derivatives were non-toxic. Interestingly, dihydroxy gamma-crotonolactone with or without substitution at the 5-position also exhibited toxicity. These results suggest that the underlying criterion for AA toxicity resides in dihydroxy gamma-crotonolactone moiety. Either substitution in the hydroxy groups or saturating the double bond render the molecule inactive.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Jan
|
| pubmed:issn |
0304-3835
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
9
|
| pubmed:volume |
122
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
93-9
|
| pubmed:dateRevised |
2003-11-14
|
| pubmed:meshHeading |
pubmed-meshheading:9464496-Animals,
pubmed-meshheading:9464496-Antineoplastic Agents,
pubmed-meshheading:9464496-Ascorbic Acid,
pubmed-meshheading:9464496-Leukemia P388,
pubmed-meshheading:9464496-Mice,
pubmed-meshheading:9464496-Structure-Activity Relationship,
pubmed-meshheading:9464496-Tumor Cells, Cultured
|
| pubmed:year |
1998
|
| pubmed:articleTitle |
Growth suppression of malignant leukemia cell line in vitro by ascorbic acid (vitamin C) and its derivatives.
|
| pubmed:affiliation |
Linus Pauling Institute of Science and Medicine, Palo Alto, CA 94306, USA.
|
| pubmed:publicationType |
Journal Article
|