Linked Life Data

18782041

Source:http://linkedlifedata.com/resource/pubmed/id/18782041

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2008-9-10
pubmed:abstractText
Malaria is one of the foremost public health problems in developing countries affecting nearly 40% of the global population. Apart from this, the past two decade's emergence of drug resistance has severely limited the choice of available antimalarial drugs. Furthermore, the general trend emerging from the SAR-studies is that chloroquine resistance does not involve any change to the target of this class of drugs but involves compound specific efflux mechanism. Based on this premise a number of groups have developed short chain analogues of 4-aminoquinoline, which are active against CQ-resistant strains of P. falciparum in in vitro studies. However, these derivatives undergo biotransformation (de-alklyation) significantly affecting lipid solubility of the drug. In view of this background information, we thought that it would be interesting to study the effect of additional lipophilicity and cationic charge at the lateral side chain of 4-aminoquinoline. This prompted us to explore the cationic amino acid conjugates namely, lysine and ornithine of 4-aminoquinoline with a view to achieve improved antimalarial activity and to the best of our knowledge such amino acid conjugates have not been hitherto reported in the literature in the case of 4-aminoquinolines. In the present study, a new series of side-chain modified 4-aminoquinolines have been synthesized and found active against both susceptible and multidrug resistant strains of P. falciparum in vitro and P. yoelli in vivo. The seminal finding of the present study is that a new series of compounds having significantly more activity against CQ resistant parasites has been identified.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1573-4064
pubmed:author
pubmed:issnType
Print
pubmed:volume
4
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
446-56
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Synthesis and antimalarial activity of novel side chain modified antimalarial agents derived from 4-aminoquinoline.
pubmed:affiliation
Division of Medicinal and Process Chemistry, Central Drug Research Institute, Lucknow 226 001, India.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't