Linked Life Data

12654761

Source:http://linkedlifedata.com/resource/pubmed/id/12654761

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2003-4-3
pubmed:abstractText
Microtubule inhibitors from several chemical classes can block the growth and development of malarial parasites, reflecting the importance of microtubules in various essential parasite functions. With the spread of antimalarial drug resistance, there is an urgent need for new approaches to the chemotherapy of this devastating disease. We investigated the effects of two naturally occurring marine peptides, dolastatin 10 and dolastatin 15, and 10 synthetic dolastatin 10-based compounds (auristatins), on cultured malarial parasites of the species most lethal to humans, Plasmodium falciparum. Dolastatin 10 was a more potent inhibitor of P. falciparum than any other previously described microtubule inhibitor, with a median inhibitory concentration (IC50) of 10-10 M. Dolastatin 15 was less active, and compounds of the auristatin series had various potencies. Comparison of the concentrations required to inhibit P. falciparum and mammalian cell proliferation showed that the orders of potency were not the same. Dolastatin 10 and auristatin PE caused arrested nuclear division and apparent disassembly of mitotic microtubular structures in the parasite. The effects of these agents were, superficially at least, similar to those of vinblastine but different from those of paclitaxel. These studies indicate that compounds binding in the 'Vinca domain' of tubulin can be highly potent antimalarial agents.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0305-7453
pubmed:author
pubmed:issnType
Print
pubmed:volume
51
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
833-41
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Effects of the antimitotic natural product dolastatin 10, and related peptides, on the human malarial parasite Plasmodium falciparum.
pubmed:affiliation
Department of Microbiology, Moyne Institute, Trinity College, Dublin 2, Ireland.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't