On April 25, 2018, Gur, Zehra Tugce; Caliskan, Burcu; Garscha, UIrike; Olgac, Abdurrahman; Schubert, Ulrich S.; Gerstmeier, Jana; Werz, Oliver; Banoglu, Erden published an article.Formula: C6H5ClN2O4S The title of the article was Identification of multi-target inhibitors of leukotriene and prostaglandin E2 biosynthesis by structural tuning of the FLAP inhibitor BRP-7. And the article contained the following:
Leukotrienes (LTs) and prostaglandin (PG)E2 are enzymically produced from arachidonic acid and represent highly bioactive lipid mediators with pro-inflammatory functions. Here, the authors report on novel multi-target inhibitors that potently and dually interfere with 5-lipoxygenase-activating protein (FLAP) and microsomal prostaglandin E2 synthase (mPGES)-1 in LT and PGE2 biosynthesis, based on the previously identified selective FLAP inhibitor BRP-7 (8, IC50 = 0.31 μM). C -substitution of the benzimidazole ring of BRP-7 by carboxylic acid and its bioisosteres provided compounds, exemplified by 57 (5-{1-[(2-chlorophenyl)methyl]-2-{1-[4-(2-methylpropyl)phenyl]ethyl}-1H-benzimidazol-5-yl}-2,3-dihydro-1,3,4-oxadiazole-2-thione) that potently suppress LT formation (IC50 = 0.05 μM) by targeting FLAP along with inhibition of mPGES-1 (IC50 = 0.42 μM). Besides FLAP, also 5-lipoxygenase (5-LO) and LTC4 synthase activities were inhibited by 57, albeit with lower potency (IC50 = 0.6 and 6.2 μM) than FLAP. Docking studies and mol. dynamic simulations with FLAP, mPGES-1 and 5-LO provide valuable insights into potential binding interactions of the inhibitors with their targets. Together, these novel benzimidazole derivatives may possess potential as leads for development of effective anti-inflammatory drugs with multi-target properties for dually inhibiting LT and PGE2 production The experimental process involved the reaction of 3-Nitro-4-chlorobenzenesulfonamide(cas: 97-09-6).Formula: C6H5ClN2O4S
The Article related to multitarget inhibitor leukotriene prostaglandin e2 flap brp7 analog preparation, 5-lipoxygenase, 5-lipoxygenase-activating protein, benzimidazole, inflammation, leukotriene, microsomal prostaglandin e(2) synthase-1 and other aspects.Formula: C6H5ClN2O4S
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