Inhibitory activities and inhibition specificities of caffeic acid derivatives and related compounds toward 5-lipoxygenase.
Various caffeic acid derivatives were synthesized, and their effects on 5-lipoxygenase (5-LO), 12-lipoxygenase (12-LO) and prostaglandin (PG) synthase activities were investigated. Among them, caffeic acid octyl amide (5) and 1-(3,4-dihydroxyphenyl)-1-octen-3-one (11) showed very potent inhibitory activities toward 5-LO with IC50 values of 4.2 x 10(-8) and 3.5 x 10(-8) M, respectively. They were very selective inhibitors for 5-LO. Compound 11 showed non-competitive inhibition, and the two adjacent hydroxy groups attached to the benzene ring, as well as the hydrophobic alkyl side chain, were required for its strong binding to 5-LO.
M
M
Sugiura
Y
Y
Naito
Y
Y
Yamaura
C
C
Fukaya
K
K
Yokoyama
D000818:Animals; D001091:Arachidonate Lipoxygenases / Q000037:antagonists & inhibitors*; D002109:Caffeic Acids / Q000138:chemical synthesis / Q000494:pharmacology*; D055598:Chemical Phenomena; D002621:Chemistry; D002934:Cinnamates / Q000494:pharmacology*; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D016859:Lipoxygenase Inhibitors
D002109:Caffeic Acids; D002934:Cinnamates; D016859:Lipoxygenase Inhibitors; D001091:Arachidonate Lipoxygenases