Dual inhibition of nitric oxide and prostaglandin E-2 production by polysubstituted 2-aminopyrimidines
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388971%3A_____%2F16%3A00464830" target="_blank" >RIV/61388971:_____/16:00464830 - isvavai.cz</a>
Alternative codes found
RIV/68378041:_____/16:00459500 RIV/61388963:_____/16:00459500
Result on the web
<a href="http://dx.doi.org/10.1016/j.niox.2016.04.008" target="_blank" >http://dx.doi.org/10.1016/j.niox.2016.04.008</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.niox.2016.04.008" target="_blank" >10.1016/j.niox.2016.04.008</a>
Alternative languages
Result language
angličtina
Original language name
Dual inhibition of nitric oxide and prostaglandin E-2 production by polysubstituted 2-aminopyrimidines
Original language description
The present in vitro experiments demonstrate inhibitory effects of polysubstituted 2-aminopyrimidines on high output production of nitric oxide (NO) and prostaglandin E-2 (PGE(2)) stimulated by interferon-gamma and lipopolysaccharide (LPS) in peritoneal macrophages of mouse and rat origin. PGE(2) production was inhibited also in LPS-activated human peripheral blood mononuclear cells. A tight dependence of the suppressive activities on chemical structure of pyrimidines was observed. Derivatives containing hydroxyl groups at the C-4 and C-6 positions of pyrimidine ring were devoid of any influence on NO and PGE(2). Remarkable inhibitory potential was acquired by the replacement of hydroxyl groups with chlorine, the 4,6-dichloro derivatives being more effective than the monochloro analogues. The effects were further intensified by modification of the amino group at the C-2 position, changing it to the (N,N-dimethylamino)methyleneamino or the formamido ones. There was no substantial difference in the expression of NO-inhibitory effects among derivatives containing distinct types of substituents at the C-5 position (hydrogen, methyl, ethyl, propyl, butyl, phenyl, and benzyl). In contrast to NO, larger substituents then methyl were required to inhibit PGE(2) production. Overall, no significant correlation between the extent of NO and PGE(2) suppression was observed. The IC(50)s of derivatives with the strongest effects on both NO and PGE(2) were within the range of 2-10 mu M. Their NO-inhibitory potential of pyrimidines was stronger than that of non-steroidal anti-inflammatory drugs (NSAIDs) aspirin and indomethacin.
Czech name
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Czech description
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Classification
Type
J<sub>x</sub> - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)
CEP classification
EE - Microbiology, virology
OECD FORD branch
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Result continuities
Project
<a href="/en/project/GAP303%2F12%2F0172" target="_blank" >GAP303/12/0172: Structure-activity relationship (SAR) study of immunosuppressive effects of pyrimidine analogues</a><br>
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2016
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Nitric Oxide-Biology and Chemistry
ISSN
1089-8603
e-ISSN
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Volume of the periodical
57
Issue of the periodical within the volume
July 1
Country of publishing house
US - UNITED STATES
Number of pages
9
Pages from-to
48-56
UT code for WoS article
000377735200006
EID of the result in the Scopus database
2-s2.0-84966716371