51515-28-7Relevant academic research and scientific papers
Synthesis and SAR studies of 3-allyl-4-prenyloxyaniline amides as potent 15-lipoxygenase inhibitors
Jabbari, Atena,Davoodnejad, Mahdieh,Alimardani, Maliheh,Assadieskandar, Amir,Sadeghian, Ali,Safdari, Hadi,Movaffagh, Jebraeel,Sadeghian, Hamid
, p. 5518 - 5526 (2012/10/30)
15-Lipoxygenases are one of the nonheme iron-containing proteins with ability of unsaturated lipid peroxidation in animals and plants. The critical role of the enzymes in formation of inflammations, sensitivities and some of cancers has been demonstrated in mammalians. Importance of the 15-lipoxygenases leads to development of mechanistic studies, products analysis and synthesis of their inhibitors. In this work new series of the 3-allyl-4-allyoxyaniline amides and 3-allyl-4-prenyloxyaniline amides were designed, synthesized and their inhibitory potency against soybean 15-lipoxygenase were determined. Among the synthetic amides, 3-allyl-4-(farnesyloxy)-adamantanilide showed the most potent inhibitory activity by IC50 value of 0.69 μM. SAR studies showed that in spite of prenyl length increases, the effects of the amide size and its electronic properties on the inhibitory potency became predominant. The SAR studies was also showed that the orientation of allyl and prenyloxy moieties toward Fe core of the SLO active site pocket is the most suitable location for enzyme inhibition.
Design, synthesis and SAR studies of 4-allyoxyaniline amides as potent 15-lipoxygensae inhibitors
Seyedi, Seyed Mohammad,Jafari, Zeinab,Attaran, Neda,Sadeghian, Hamid,Saberi, Mohammad Reza,Riazi, Mohammad Mahdi
experimental part, p. 1614 - 1622 (2009/08/15)
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 IC50 in SLO inhibition (IC50 = 0.67 ± 0.06 μM). 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 Fe3+-OH moiety in the active site of enzyme and fixed by hydrogen bonding with two conserved His513 and Gln716. 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.
