Dual inhibition of nitric oxide and prostaglandin E-2 production by polysubstituted 2-aminopyrimidines

Kód výsledku v 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>

Nalezeny alternativní kódy

RIV/68378041:_____/16:00459500 RIV/61388963:_____/16:00459500

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

Dual inhibition of nitric oxide and prostaglandin E-2 production by polysubstituted 2-aminopyrimidines

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

Dual inhibition of nitric oxide and prostaglandin E-2 production by polysubstituted 2-aminopyrimidines

Popis výsledku anglicky

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.

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

EE - Mikrobiologie, virologie

OECD FORD obor

—

Projekt

<a href="/cs/project/GAP303%2F12%2F0172" target="_blank" >GAP303/12/0172: Studie vztahu mezi strukturou a imunosupresivní aktivitou pyrimidinových analogů</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2016

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Nitric Oxide-Biology and Chemistry

ISSN

1089-8603

e-ISSN

—

Svazek periodika

57

Číslo periodika v rámci svazku

July 1

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

9

Strana od-do

48-56

Kód UT WoS článku

000377735200006

EID výsledku v databázi Scopus

2-s2.0-84966716371