- Pyrazol-3-propanoic acid derivatives as novel inhibitors of leukotriene biosynthesis in human neutrophils
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We recently presented that compounds 4a-b moderately inhibited leukotriene (LT) formation in human neutrophils. For structural derivatization of 4a-b, novel thirty-six title compounds were synthesized and led to more potent inhibition of LT biosynthesis in activated human neutrophils exemplified by compounds 15, 27-30, 32-37, 41, 42 with IC50 values in the range of 1.6-3.5 μM. Moreover, compounds 32, 35, 42, 43 and 44 showed a substantial inhibition of platelet COX-1 activity with IC50 of 2.5, 0.041, 0.3, 0.9 and 0.014 μM, respectively, leading up to dual acting inhibitors. On the basis of their high potency in cellular environment, these straightforward pyrazole-3-propanoic acid derivatives may possess potential in the design of more potent compounds for intervention with inflammatory and allergic diseases.
- ?ali?kan, Burcu,Luderer, Susann,?zkan, Ya?mur,Werz, Oliver,Banoglu, Erden
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p. 5021 - 5033
(2011/11/30)
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- Synthesis of 1,5-diarylpyrazol-3-propanoic acids towards inhibition of cyclooxygenase-1/2 activity and 5-lipoxygenase-mediated LTB4 formation
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A set of 25 derivatives of 3-[1-(6-substituted-pyridazin-3-yl)-5-(4- substitutedphenyl)-1H-pyrazol-3-yl]propanoic acids has been synthesized and evaluated for their in vitro cyclooxygenase-1/2 (COX-1/ 2) inhibitory activity using assays with purified COX-1 and COX-2 enzymes as well as for their 5-lipoxygenase (5-LO)-mediated LTB4 formation inhibitory activity using an assay with activated human polymorphonuclear leukocytes (PMNL). Among the synthesized compounds, especially 4g showed COX-1 (IC50 = 1.5 μM) and COX-2 (IC50 = 1.6 μM) inhibitory activity, whereas compounds 4b and 4 f resulted in the inhibition of 5-LO-mediated LTB4 formation at 14 μM and 12 μM IC50 values, respectively, without any significant inhibition on COX isoforms. ECV · Editio Cantor Verlag.
- Erguen, Burcu Caliskan,Nunez, Maria Teresa,Labeaga, Luis,Ledo, Francisco,Darlington, Janice,Bain, Gretchen,Cakir, Bilge,Banoglu, Erden
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p. 497 - 505
(2011/05/09)
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