title: Design, synthesis and SAR studies of 4-allyoxyaniline amides as potent 15-lipoxygensae inhibitors.
abstract: A group of 4-allyloxyaniline amides 5a-o were designed, synthesized and evaluated as potential inhibitors of soybean 15-lipoxygenase (SLO) on the basis of eugenol and esteragol structures. Compound 5e showed the best IC(50) in SLO inhibition (IC(50)=0.67+/-0.06 microM). All compounds were docked in SLO active site retrieved from RCSB Protein Data Bank (PDB entry: 1IK3) and showed that allyloxy group of compounds is oriented towards the Fe(3+)-OH moiety in the active site of enzyme and fixed by hydrogen bonding with two conserved His(513) and Gln(716). It is resulted that molecular volume of the amide moiety would be a major factor in inhibitory potency variation of the synthetic amides, where the hydrogen bonding of the amide group could also involve in the activity of the inhibitors.
authors.affiliation: Department of Chemistry, Faculty of Sciences, Ferdowsi University of Mashhad, Mashhad, Islamic Republic of Iran. smseyedi@yahoo.com
authors.forename: Seyed Mohammad
authors.initials: SM
authors.lastname: Seyedi
authors.forename: Hossein
authors.initials: H
authors.lastname: Eshghi
authors.forename: Zeinab
authors.initials: Z
authors.lastname: Jafari
authors.forename: Neda
authors.initials: N
authors.lastname: Attaran
authors.forename: Hamid
authors.initials: H
authors.lastname: Sadeghian
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Saberi
authors.forename: Mohammad Mahdi
authors.initials: MM
authors.lastname: Riazi
mesh_terms: D000814:Aniline Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D015195:Drug Design; D004952:Esters / Q000737:chemistry; D005054:Eugenol / Q000031:analogs & derivatives / Q000737:chemistry; D016859:Lipoxygenase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D008958:Models, Molecular; D008968:Molecular Conformation; D013329:Structure-Activity Relationship
chemical_list: D000814:Aniline Compounds; D004952:Esters; D016859:Lipoxygenase Inhibitors; D005054:Eugenol