Synthesis of 1,5-diarylpyrazol-3-propanoic acids towards inhibition of cyclooxygenase-1/2 activity and 5-lipoxygenase-mediated LTB4 formation

Burcu Çalişkan Ergün; Maria Teresa Nuñez; Luis Labeaga; Francisco Ledo; Janice Darlington; Gretchen Bain; Bilge Çakir; Erden Banoglu

doi:10.1055/s-0031-1296318

Synthesis of 1,5-diarylpyrazol-3-propanoic acids towards inhibition of cyclooxygenase-1/2 activity and 5-lipoxygenase-mediated LTB₄ formation

Burcu Çalişkan Ergün
, Maria Teresa Nuñez
, Luis Labeaga
, Francisco Ledo
, Janice Darlington
, Gretchen Bain
, Bilge Çakir
, Erden Banoglu^*

^*Corresponding author for this work

Gazi University
Departamanto de Investigacion
Amira Pharmaceuticals

Research output: Contribution to journal › Article › peer-review

16 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	497-505
Number of pages	9
Journal	Arzneimittel-Forschung/Drug Research
Volume	60
Issue number	8
DOIs	https://doi.org/10.1055/s-0031-1296318
Publication status	Published - 2010
Externally published	Yes

Keywords

Aryl propanoic acids
COX-1/2 inhibitors
Leukotriene B
Pyrazole

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10.1055/s-0031-1296318

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title = "Synthesis of 1,5-diarylpyrazol-3-propanoic acids towards inhibition of cyclooxygenase-1/2 activity and 5-lipoxygenase-mediated LTB4 formation",

abstract = "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.",

keywords = "Aryl propanoic acids, COX-1/2 inhibitors, Leukotriene B, Pyrazole",

author = "Erg{\"u}n, \{Burcu {\c C}ali{\c s}kan\} and Nu{\~n}ez, \{Maria Teresa\} and Luis Labeaga and Francisco Ledo and Janice Darlington and Gretchen Bain and Bilge {\c C}akir and Erden Banoglu",

year = "2010",

doi = "10.1055/s-0031-1296318",

language = "English",

volume = "60",

pages = "497--505",

journal = "Arzneimittel-Forschung/Drug Research",

issn = "0004-4172",

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TY - JOUR

T1 - Synthesis of 1,5-diarylpyrazol-3-propanoic acids towards inhibition of cyclooxygenase-1/2 activity and 5-lipoxygenase-mediated LTB4 formation

AU - Ergün, Burcu Çalişkan

AU - Nuñez, Maria Teresa

AU - Labeaga, Luis

AU - Ledo, Francisco

AU - Darlington, Janice

AU - Bain, Gretchen

AU - Çakir, Bilge

AU - Banoglu, Erden

PY - 2010

Y1 - 2010

N2 - 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.

AB - 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.

KW - Aryl propanoic acids

KW - COX-1/2 inhibitors

KW - Leukotriene B

KW - Pyrazole

UR - https://www.scopus.com/pages/publications/77956371766

U2 - 10.1055/s-0031-1296318

DO - 10.1055/s-0031-1296318

M3 - Article

C2 - 20863006

AN - SCOPUS:77956371766

SN - 0004-4172

VL - 60

SP - 497

EP - 505

JO - Arzneimittel-Forschung/Drug Research

JF - Arzneimittel-Forschung/Drug Research

IS - 8

ER -

Synthesis of 1,5-diarylpyrazol-3-propanoic acids towards inhibition of cyclooxygenase-1/2 activity and 5-lipoxygenase-mediated LTB₄ formation

Abstract

Keywords

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