New bis-catechols 5-lipoxygenase inhibitors.
Three polyhydroxy-2-phenylnaphthalenes (1-3) and the oxy analogue of tetrahydroxypavinan (4) were prepared and evaluated for their antioxidant properties (inhibition of diphenylpycrylhydrazyl radical (DPPH), reduction of iron (III) ion) and inhibition of 5-lipoxygenase (5-LO) activity. Their three-dimensional structures were established on the basis of spectroscopic data and semiempirical calculations. Compounds 1 and 2 were found as potent 5-LO inhibitors as nordihydroguaiaretic acid (NDGA), whereas 4 is 2.5 times less potent than NDGA. The reliability of the 3-D structures with the 5-LO inhibition properties is discussed. Their antioxidant properties show that tested compounds are expected to act as redox inhibitors.
Dupont
R
R
Laboratoire de Chimie Organique et Macromoléculaire, UPRESA CNRS 8009, Villeneuve d'Ascq, France.
Goossens
J F
JF
Cotelle
N
N
Vrielynck
L
L
Vezin
H
H
Hénichart
J P
JP
Cotelle
P
P
D000818:Animals; D000975:Antioxidants / Q000138:chemical synthesis / Q000494:pharmacology; D001094:Arachidonate 5-Lipoxygenase / Q000187:drug effects* / Q000378:metabolism; D015764:Bepridil / Q000031:analogs & derivatives* / Q000378:metabolism; D001713:Biphenyl Compounds; D002396:Catechols; D007202:Indicators and Reagents; D007501:Iron / Q000378:metabolism; D007700:Kinetics; D016859:Lipoxygenase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D015394:Molecular Structure; D010084:Oxidation-Reduction; D010851:Picrates; D051381:Rats; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D000975:Antioxidants; D001713:Biphenyl Compounds; D002396:Catechols; D007202:Indicators and Reagents; D016859:Lipoxygenase Inhibitors; D010851:Picrates; D015764:Bepridil; C004931:1,1-diphenyl-2-picrylhydrazyl; D007501:Iron; D001094:Arachidonate 5-Lipoxygenase