Design and synthesis of eugenol derivatives, as potent 15-lipoxygenase inhibitors.
A group of 4-allyl-2-methoxyphenol (eugenol) esters were designed, synthesized, and evaluated as potential inhibitors of soybean 15-lipoxygenase (SLO). Compounds 4c, 4d 4f, 4p, and 4q showed the best IC(50) in SLO inhibition (IC(50)=1.7, 2.3, 2.1, 2.2, and 0.017microM, respectively). All compounds were docked into SLO active site and showed that allyl group of compounds is oriented toward the iron atom in the active site of SLO. It is assumed that lipophilic interaction of ligand-enzyme would be in charge of inhibiting the enzyme activity. The selectivity of eugenol derivatives in inhibiting 15-HLOb was also compared with 15-HLOa by molecular modeling and multiple alignment techniques.
Sadeghian
Hamid
H
Department of Chemistry, Faculty of Sciences, Ferdowsi University of Mashhad, Mashhad 91775-1436, Iran.
Seyedi
Seyed Mohammad
SM
Saberi
Mohammad Reza
MR
Arghiani
Zahra
Z
Riazi
Mehdi
M
D000596:Amino Acids / Q000737:chemistry / Q000494:pharmacology; D020650:Combinatorial Chemistry Techniques; D000075202:Contraindications; D018360:Crystallography, X-Ray; D015195:Drug Design; D005054:Eugenol / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D016859:Lipoxygenase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D021281:Quantitative Structure-Activity Relationship; D013025:Glycine max / Q000201:enzymology
D000596:Amino Acids; D016859:Lipoxygenase Inhibitors; D005054:Eugenol