Effect of imidazo[1,2-a]pyrimidine derivatives on leukocyte function.
OBJECTIVE
A series of six imidazo[1,2-a]pyrimidine (IP) derivatives were evaluated for their effects on leukocyte functions in vitro as well as on the inflammatory response induced by zymosan in the mouse air pouch.


METHODS
Human neutrophils and murine peritoneal macrophages were used for in vitro assays. Mouse air pouch was performed in Swiss mice.


METHODS
Test compounds were incubated with either human neutrophils or mouse peritoneal macrophages at concentrations not showing cytotoxic effects. For in vivo experiments, IPs were injected into the air pouch.


METHODS
Elastase and myeloperoxidase release, superoxide generation and LTB4 production were assayed in human neutrophils treated with different stimuli. Mouse peritoneal macrophages were stimulated with lipopolysaccharide (LPS), followed by determination of nitrite and PGE2 levels in supernatants. Zymosan was injected into six days-old mouse air pouches. Dunnett's t-test was employed for statistical analysis.


RESULTS
All IPs inhibited human neutrophil degranulation with IC50 values in the microM range. IP-1, IP-2 and IP-5 also decreased superoxide generation. In LPS-stimulated macrophages, IP-4 and IP-6 inhibited nitrite production with a moderate reduction in PGE2 generation. In addition, these two compounds at 100 nmol/pouch inhibited leukocyte migration and LTB4 levels in the exudate of the mouse air pouch.


CONCLUSIONS
Imidazo[1,2-a]pyrimidines are a class of compounds with antiinflammatory potential.
Vidal
A
A
Departamento de Farmacología, Universidad de Valencia, Facultad de Farmacia, Spain.
Ferrándiz
M L
ML
Ubeda
A
A
Acero-Alarcón
A
A
Sepulveda-Arques
J
J
Alcaraz
M J
MJ
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D007975:Leukotriene B4 / Q000096:biosynthesis; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000502:physiology; D051379:Mice; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology; D011743:Pyrimidines / Q000494:pharmacology*; D013481:Superoxides / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D007093:Imidazoles; D011743:Pyrimidines; D013481:Superoxides; D007975:Leukotriene B4