Design, synthesis and SAR studies of 4-allyoxyaniline amides as potent 15-lipoxygensae inhibitors.
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.
Seyedi
Seyed Mohammad
SM
Department of Chemistry, Faculty of Sciences, Ferdowsi University of Mashhad, Mashhad, Islamic Republic of Iran. smseyedi@yahoo.com
Eshghi
Hossein
H
Jafari
Zeinab
Z
Attaran
Neda
N
Sadeghian
Hamid
H
Saberi
Mohammad Reza
MR
Riazi
Mohammad Mahdi
MM
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
D000814:Aniline Compounds; D004952:Esters; D016859:Lipoxygenase Inhibitors; D005054:Eugenol