Linked Life Data

16480285

Source:http://linkedlifedata.com/resource/pubmed/id/16480285

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2006-2-16
pubmed:abstractText
A series of multifunctional codrugs (1-4), obtained by joining L-Dopa (LD) and dopamine (DA) with (R)-alpha-lipoic acid (LA), was synthesized and evaluated as potential codrugs with antioxidant and iron-chelating properties. These multifunctional molecules were synthesized to overcome the pro-oxidant effect associated with LD therapy. The physicochemical properties, together with the chemical and enzymatic stabilities of synthesized compounds, were evaluated in order to determine both their stability in aqueous medium and their sensitivity in undergoing enzymatic cleavage by rat and human plasma to regenerate the original drugs. The new compounds were tested for their radical scavenging activities, using a test involving the Fe (II)-H2O2-induced degradation of deoxyribose, and to evaluate peripheral markers of oxidative stress such as plasmatic activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx) in the plasma. Furthermore, we showed the central effects of compounds 1 and 2 on spontaneous locomotor activity of rats in comparison with LD-treated animals. From the results obtained, compounds 1-4 appeared stable at a pH of 1.3 and in 7.4 buffered solution; in 80% human plasma they were turned into DA and LD. Codrugs 1-4 possess good lipophilicity (log P > 2 for all tested compounds). Compounds 1 and 2 seem to protect partially against the oxidative stress deriving from auto-oxidation and MAO-mediated metabolism of DA. This evidence, together with the "in vivo" dopaminergic activity and a sustained release of the parent drug in human plasma, allowed us to point out the potential advantages of using 1 and 2 rather than LD in treating pathologies such as Parkinson's disease, characterized by an evident decrease of DA concentration in the brain.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:day
23
pubmed:volume
49
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1486-93
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:16480285-Animals, pubmed-meshheading:16480285-Antioxidants, pubmed-meshheading:16480285-Biological Markers, pubmed-meshheading:16480285-Dopamine, pubmed-meshheading:16480285-Dopamine Agonists, pubmed-meshheading:16480285-Drug Stability, pubmed-meshheading:16480285-Free Radical Scavengers, pubmed-meshheading:16480285-Glutathione Peroxidase, pubmed-meshheading:16480285-Humans, pubmed-meshheading:16480285-Hydrogen-Ion Concentration, pubmed-meshheading:16480285-Hydrolysis, pubmed-meshheading:16480285-Iron Chelating Agents, pubmed-meshheading:16480285-Kinetics, pubmed-meshheading:16480285-Levodopa, pubmed-meshheading:16480285-Male, pubmed-meshheading:16480285-Motor Activity, pubmed-meshheading:16480285-Oxidative Stress, pubmed-meshheading:16480285-Rats, pubmed-meshheading:16480285-Rats, Wistar, pubmed-meshheading:16480285-Solubility, pubmed-meshheading:16480285-Stereoisomerism, pubmed-meshheading:16480285-Structure-Activity Relationship, pubmed-meshheading:16480285-Superoxide Dismutase, pubmed-meshheading:16480285-Thioctic Acid
pubmed:year
2006
pubmed:articleTitle
L-dopa- and dopamine-(R)-alpha-lipoic acid conjugates as multifunctional codrugs with antioxidant properties.
pubmed:affiliation
Dipartimento di Scienze del Farmaco, Università G. D'Annunzio, Via dei Vestini 31, 66100 Chieti, Italy. adistefano@unich.it
pubmed:publicationType
Journal Article, In Vitro, Research Support, Non-U.S. Gov't