Linked Life Data

7131486

Source:http://linkedlifedata.com/resource/pubmed/id/7131486

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
1982-12-21
pubmed:abstractText
The anticancer drug etoposide (VP 16-213, 1) contains a highly strained trans-fused gamma-lactone. This functionality is readily metabolized to an inactive ring-opened hydroxy acid (2). To prevent this detoxification of the drug and to investigate whether the lactone is essential for drug activity, we synthesized a cyclic ether analogue of etoposide (3) and tested it in the mouse leukemia L1210 system in vitro and in vivo. This ether analogue of etoposide was found to retain activity in the L1210 system, but the activity was reduced relative to the parent drug. A synthetic intermediate, the ring D opened diol of the reduced lactone (4), was also tested and found to be inactive in the L1210 system. The complete 470-MHz 1H NMR spectra of etoposide and its derivatives are reported. The usefulness of introducing deuterium at C-13 to determine J2,3 is also demonstrated. This coupling constant is characteristic of cis or trans stereochemistry across the C-D ring fusion.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:volume
25
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1077-81
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
1982
pubmed:articleTitle
Synthesis, 470-MHz 1H NMR spectra, and activity of delactonized derivatives of the anticancer drug etoposide.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't