Nucleotide analogues with immunobiological properties: 9-[2-Hydroxy-3-(phosphonomethoxy)propyl]-adenine (HPMPA), -2,6-diaminopurine (HPMPDAP), and their N6-substituted derivatives
Jazyk angličtina Země Nizozemsko Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
16733050
DOI
10.1016/j.ejphar.2006.04.018
PII: S0014-2999(06)00422-5
Knihovny.cz E-zdroje
- MeSH
- adenin analogy a deriváty chemie farmakologie MeSH
- antagonisté purinergního receptoru P1 MeSH
- chinazoliny farmakologie MeSH
- cytokiny metabolismus MeSH
- dihydropyridiny farmakologie MeSH
- exprese genu genetika MeSH
- interferon gama farmakologie MeSH
- kofein analogy a deriváty farmakologie MeSH
- lipopolysacharidy farmakologie MeSH
- messenger RNA genetika metabolismus MeSH
- molekulární struktura MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- nukleotidy chemie imunologie farmakologie MeSH
- organofosfonáty chemie farmakologie MeSH
- organofosforové sloučeniny chemie farmakologie MeSH
- oxid dusnatý biosyntéza MeSH
- peritoneální makrofágy cytologie účinky léků metabolismus MeSH
- polymerázová řetězová reakce s reverzní transkripcí MeSH
- purinergní receptory P1 imunologie fyziologie MeSH
- synthasa oxidu dusnatého, typ II genetika MeSH
- triazoly farmakologie MeSH
- viabilita buněk účinky léků MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- 8-(3-chlorostyryl)caffeine MeSH Prohlížeč
- 9-(3-hydroxy-2-phosphonomethoxypropyl)-2,6-diaminopurine MeSH Prohlížeč
- 9-(S)-(3-hydroxy-2-(phosphonomethoxy)propyl)adenine MeSH Prohlížeč
- 9-chloro-2-(2-furyl)-(1,2,4)triazolo(1,5-c)quinazolin-5-imine MeSH Prohlížeč
- adenin MeSH
- antagonisté purinergního receptoru P1 MeSH
- chinazoliny MeSH
- cytokiny MeSH
- dihydropyridiny MeSH
- interferon gama MeSH
- kofein MeSH
- lipopolysacharidy MeSH
- messenger RNA MeSH
- MRS 1191 MeSH Prohlížeč
- nukleotidy MeSH
- organofosfonáty MeSH
- organofosforové sloučeniny MeSH
- oxid dusnatý MeSH
- purinergní receptory P1 MeSH
- synthasa oxidu dusnatého, typ II MeSH
- triazoly MeSH
Newly developed acyclic nucleoside phosphonates, derivatives of adenine and 2,6-diaminopurine bearing the 2-hydroxy-3-(phosphonomethoxy)propyl (HPMP) moiety at the N9-side chain (i.e., HPMPA and HPMPDAP, respectively) were screened for in vitro immunobiological activity, using mouse resident peritoneal macrophages and splenocytes. Both HPMPA and HPMPDAP augmented the interferon-gamma-triggered production of NO as well as expression of inducible nitric oxide synthase (iNOS) mRNA in macrophages. HPMPDAP activated secretion of tumor necrosis factor-alpha (TNF-alpha), chemokines "regulated-upon-activation, normal T cell expressed and secreted" (RANTES) and macrophage inflammatory protein-1alpha (MIP-1alpha), and marginally also secretion of interleukin-10 (IL-10) in both macrophages and splenocytes. The HPMPA, less prominently than HPMPDAP, elevated only secretion of RANTES and TNF-alpha. The compounds also activated secretion of TNF-alpha (HPMPDAP > HPMPA) in human peripheral blood mononuclear cells (PBMC). Distinct N6-substituted derivatives, i.e., N6-dimethyl-, N6-cyclopropyl-, N6-piperidin-1-yl-, N6-(2-methoxyethyl)-, N6-(2-hydroxyethyl)-, N6-allyl- and N6-2-(dimethylamino)ethyl-HPMPA/HPMPDAP as well as 6-thio and 6-hydroxy derivatives usually showed loss of the activity compared to the parent compounds. The immunomodulatory effects were found to be at least in part dependent on P1 purinoreceptors, and mediated by transcriptional factor nuclear factor-kappaB.
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