1-(6-Hydroxy-2-isopropenyl-1-benzofuran-5-yl)1-ethanone
(1), isolated from the roots of Petasites hybridus
L., and a series of synthetic benzoxazepine derivatives of
compound 1(2–6) were evaluated for their immunomodulatory
effects. The compounds were evaluated for their effects
on the respiratory burst of human whole blood and isolated
human polymorphonuclear leukocytes (PMNs) using luminol-
and lucigenin-based chemiluminescence (CL) assays,
and their effect on chemotactic migration of PMNs was
assessed using the Boyden chamber technique. Compound 1
exhibited stronger inhibition than acetylsalicylic acid (ASA)
on luminol-enhanced CL of PMNs. It also inhibited PMN
chemotaxis with an IC
value comparable to that of ibuprofen.
Of the compounds tested, 5 was the most effective in
inhibiting luminol-enhanced CL and also strongly inhibited
lucigenin-enhanced CL with IC
50
values lower than that of
ASA. Compound 2 was the most active in inhibiting migration
of PMNs and was five times stronger than ibuprofen. The
results suggest that compound 1 and its synthesizedbenzoxazepine derivatives, especially compounds 2 and 5,
were able to modulate the innate immune response of
phagocytes at different steps, emphasizing their potential
as leads for the development of new immunomodulatory
agents.
