Linked Life Data

18805011

Source:http://linkedlifedata.com/resource/pubmed/id/18805011

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
19
pubmed:dateCreated
2008-10-17
pubmed:abstractText
In recent years polycyclic compounds have been shown to exhibit pharmacological profiles of importance in the symptomatic and proposed curative treatment of neurodegenerative diseases (e.g., Parkinson's and Alzheimer's disease). These structures also show modification and improvement of the pharmacokinetic and pharmacodynamic properties of drugs in current use. Nitric oxide (NO) is a molecular messenger involved in a number of physiological processes in mammals. It is synthesised by nitric oxide synthase (NOS) from L-arginine and its overproduction could lead to a number of neurological disorders. The aim of this study was to synthesise a series of novel indazole, indole and other fluorescent derivatives conjugated to polycyclic structures for evaluation in NOS assays. NOS is a target system where fluorescent techniques and fluorescently labelled NOS inhibitors can be used for detecting the biophysical properties of enzyme-ligand interactions and thus facilitate development of novel inhibitors of neurodegeneration. This could lead to a greater insight into the neuroprotective mechanism and a possible cure/treatment for neurodegenerative diseases. A series of compounds incorporating polycyclic structures such as 3-hydroxy-4-aza-8-oxoheptacyclo[9.4.1.0.(2,10)0.(3,14)0.(4,9)0.(9,13)0(12,15)]tetradecane and amantadine as well as suitable fluorescent moieties were selected for synthesis. In the biological evaluation the oxyhaemoglobin (oxyHb) assay was employed to determine the activity of the novel compounds at an enzymatic level of NOS. IC(50) values of the novel fluorescent compounds were compared to that of aminoguanidine (AG) and 7-nitroindazole (7-NI), two known NOS inhibitors, and showed moderate to high affinity (IC(50) values ranging from 7.73 microM to 0.291 microM) for the NOS enzyme.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1464-3391
pubmed:author
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
16
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
8952-8
pubmed:meshHeading
pubmed-meshheading:18805011-Alkanes, pubmed-meshheading:18805011-Amantadine, pubmed-meshheading:18805011-Animals, pubmed-meshheading:18805011-Aza Compounds, pubmed-meshheading:18805011-Biological Assay, pubmed-meshheading:18805011-Enzyme Inhibitors, pubmed-meshheading:18805011-Fluorescent Dyes, pubmed-meshheading:18805011-Ligands, pubmed-meshheading:18805011-Male, pubmed-meshheading:18805011-Neurodegenerative Diseases, pubmed-meshheading:18805011-Neuroprotective Agents, pubmed-meshheading:18805011-Nitric Oxide Synthase, pubmed-meshheading:18805011-Oxyhemoglobins, pubmed-meshheading:18805011-Polycyclic Hydrocarbons, Aromatic, pubmed-meshheading:18805011-Rats, pubmed-meshheading:18805011-Rats, Sprague-Dawley, pubmed-meshheading:18805011-Spectrometry, Fluorescence, pubmed-meshheading:18805011-Structure-Activity Relationship
pubmed:year
2008
pubmed:articleTitle
Fluorescent polycyclic ligands for nitric oxide synthase (NOS) inhibition.
pubmed:affiliation
Pharmaceutical Chemistry, School of Pharmacy, North-West University, Private Bag 6001, Potchefstroom 2520, South Africa.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't