PMID- 8147901
OWN - NLM
STAT- MEDLINE
DCOM- 19940505
LR  - 20190623
IS  - 0006-2952 (Print)
IS  - 0006-2952 (Linking)
VI  - 47
IP  - 6
DP  - 1994 Mar 15
TI  - Contrasting effects of two arachidonate 5-lipoxygenase inhibitors on 
      formyl-methionyl-leucyl-phenylalanine (fMLP) and complement fragment 5a induced 
      human neutrophil superoxide generation.
PG  - 1029-37
AB  - SC-45662 and SC-41661A, selective arachidonate 5-lipoxygenase (5-LO) inhibitors, 
      had markedly different effects on formyl-methionyl-leucyl-phenylalanine (fMLP) 
      and complement fragment 5a (C5a) induced superoxide release from human 
      neutrophils (PMNs). SC-45662 inhibited superoxide generation induced by fMLP and 
      C5a with IC50 values of 12 and 5 microM, respectively. Furthermore, SC-45662 was 
      capable of inhibiting fMLP and C5a induced superoxide release in PMNs primed with 
      bacterial lipopolysaccharide, tumor necrosis factor-alpha and other priming 
      agents. SC-41661A, a compound from the same chemical series as SC-45662, did not 
      inhibit or induce superoxide generation, but instead primed PMNs for fMLP and C5a 
      induced superoxide generation. The induced superoxide release was concentration 
      dependently enhanced 2 to 4-fold at 5-50 microM. Superoxide release induced by 
      phorbol myristate acetate or serum-activated zymosan was unaffected by either 
      SC-45662 or SC-41661A. The regulation of superoxide generation by these 
      compounds, both of which have the identical oxidation-reduction pharmacophore, 
      was clearly independent of their effects on 5-LO activity. Furthermore, the 
      mechanism by which SC-45662 and SC-41661A alter superoxide generation did not 
      appear to depend on inhibition of xanthine oxidase, catalase or superoxide 
      dismutase. These new compounds provide effective tools for further investigation 
      of the relationship of these two biochemical oxidative systems.
FAU - Kocan, G P
AU  - Kocan GP
AD  - Infectious Diseases Research Department, Searle Research and Development, Skokie, 
      IL 60077.
FAU - Partis, R A
AU  - Partis RA
FAU - Mueller, R A
AU  - Mueller RA
FAU - Smith, W G
AU  - Smith WG
FAU - Nakao, A
AU  - Nakao A
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PL  - England
TA  - Biochem Pharmacol
JT  - Biochemical pharmacology
JID - 0101032
RN  - 0 (Acetates)
RN  - 0 (Amides)
RN  - 0 (Lipoxygenase Inhibitors)
RN  - 0 (Phenols)
RN  - 0 (Pyridines)
RN  - 11062-77-4 (Superoxides)
RN  - 137803-61-3 ((2-((3,5-di-t-butyl-4-hydroxyphenyl)thio)-1-methylpropoxy)acetic 
      acid)
RN  - 148047-03-4 (SC 41661A)
RN  - 59880-97-6 (N-Formylmethionine Leucyl-Phenylalanine)
RN  - 80295-54-1 (Complement C5a)
SB  - IM
MH  - Acetates/pharmacology
MH  - Amides/pharmacology
MH  - Animals
MH  - Complement C5a/*pharmacology
MH  - Humans
MH  - *Lipoxygenase Inhibitors/pharmacology
MH  - N-Formylmethionine Leucyl-Phenylalanine/*pharmacology
MH  - Neutrophils/*drug effects/metabolism
MH  - Phenols/pharmacology
MH  - Pyridines/pharmacology
MH  - Rats
MH  - Superoxides/*blood
MH  - Tumor Cells, Cultured
EDAT- 1994/03/15 00:00
MHDA- 1994/03/15 00:01
CRDT- 1994/03/15 00:00
PHST- 1994/03/15 00:00 [pubmed]
PHST- 1994/03/15 00:01 [medline]
PHST- 1994/03/15 00:00 [entrez]
AID - 0006-2952(94)90414-6 [pii]
AID - 10.1016/0006-2952(94)90414-6 [doi]
PST - ppublish
SO  - Biochem Pharmacol. 1994 Mar 15;47(6):1029-37. doi: 10.1016/0006-2952(94)90414-6.