Inhibitory effects of triarylpyrazole derivatives on LPS-induced nitric oxide and PGE2 productions in murine RAW 264.7 macrophages

Mahmoud M. Gamal El-Din; Mohammed I. El-Gamal; Mohammed S. Abdel-Maksoud; Huijeong Lee; Jungseung Choi; Tae Woo Kim; Ji Sun Shin; Hwi Ho Lee; Hee Kwon Kim; Kyung Tae Lee; Daejin Baek

doi:10.1016/j.bmcl.2019.126884

Inhibitory effects of triarylpyrazole derivatives on LPS-induced nitric oxide and PGE₂ productions in murine RAW 264.7 macrophages

Mahmoud M. Gamal El-Din
, Mohammed I. El-Gamal
, Mohammed S. Abdel-Maksoud
, Huijeong Lee
, Jungseung Choi
, Tae Woo Kim
, Ji Sun Shin
, Hwi Ho Lee
, Hee Kwon Kim
, Kyung Tae Lee^*
, Daejin Baek

^*Corresponding author for this work

Department of Medicine

Research output: Contribution to journal › Journal article › peer-review

11 Scopus citations

Abstract

In this article, a series of 22 triarylpyrazole derivatives were evaluated for in vitro antiinflammatory activity as inhibitors of nitric oxide (NO) and prostaglandin E₂ (PGE₂) release induced by lipopolysaccharide (LPS) in murine RAW 264.7 macrophages. The synthesized compounds 1a-h, 2a-f and 3a-h were first examined for their cytotoxicity for determination of the non-toxic concentration for antiinflammatory screening, so that the inhibitory effects against NO and PGE₂ production were not caused by non-specific cytotoxicity. Compounds 1h and 2f were the most active PGE₂ inhibitors with IC₅₀ values of 2.94 μM and 4.21 μM, respectively. Western blotting and cell-free COX-2 screening revealed that their effects were due to inhibition of COX-2 protein expression. Moreover, compound 1h exerted strong inhibitory effect on the expression of COX-2 mRNA in LPS-induced murine RAW 264.7 macrophages.

Original language	English
Article number	126884
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	30
Issue number	4
DOIs	https://doi.org/10.1016/j.bmcl.2019.126884
State	Published - 2020.02.15

Keywords

Amide
Antiinflammatory
COX-2
iNOS
NO
PGE
Triarylpyrazole
Urea

Quacquarelli Symonds(QS) Subject Topics

Medicine
Engineering - Petroleum
Pharmacy & Pharmacology
Chemistry
Biological Sciences

Access to Document

10.1016/j.bmcl.2019.126884

Cite this

Gamal El-Din, M. M., El-Gamal, M. I., Abdel-Maksoud, M. S., Lee, H., Choi, J., Kim, T. W., Shin, J. S., Lee, H. H., Kim, H. K., Lee, K. T., & Baek, D. (2020). Inhibitory effects of triarylpyrazole derivatives on LPS-induced nitric oxide and PGE₂ productions in murine RAW 264.7 macrophages. Bioorganic and Medicinal Chemistry Letters, 30(4), Article 126884. https://doi.org/10.1016/j.bmcl.2019.126884

@article{27cb07de5314437f9e116735b01664fa,

title = "Inhibitory effects of triarylpyrazole derivatives on LPS-induced nitric oxide and PGE2 productions in murine RAW 264.7 macrophages",

abstract = "In this article, a series of 22 triarylpyrazole derivatives were evaluated for in vitro antiinflammatory activity as inhibitors of nitric oxide (NO) and prostaglandin E2 (PGE2) release induced by lipopolysaccharide (LPS) in murine RAW 264.7 macrophages. The synthesized compounds 1a-h, 2a-f and 3a-h were first examined for their cytotoxicity for determination of the non-toxic concentration for antiinflammatory screening, so that the inhibitory effects against NO and PGE2 production were not caused by non-specific cytotoxicity. Compounds 1h and 2f were the most active PGE2 inhibitors with IC50 values of 2.94 μM and 4.21 μM, respectively. Western blotting and cell-free COX-2 screening revealed that their effects were due to inhibition of COX-2 protein expression. Moreover, compound 1h exerted strong inhibitory effect on the expression of COX-2 mRNA in LPS-induced murine RAW 264.7 macrophages.",

keywords = "Amide, Antiinflammatory, COX-2, iNOS, NO, PGE, Triarylpyrazole, Urea",

author = "\{Gamal El-Din\}, \{Mahmoud M.\} and El-Gamal, \{Mohammed I.\} and Abdel-Maksoud, \{Mohammed S.\} and Huijeong Lee and Jungseung Choi and Kim, \{Tae Woo\} and Shin, \{Ji Sun\} and Lee, \{Hwi Ho\} and Kim, \{Hee Kwon\} and Lee, \{Kyung Tae\} and Daejin Baek",

note = "Publisher Copyright: {\textcopyright} 2019 Elsevier Ltd",

year = "2020",

month = feb,

day = "15",

doi = "10.1016/j.bmcl.2019.126884",

language = "English",

volume = "30",

journal = "Bioorganic and Medicinal Chemistry Letters",

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Gamal El-Din, MM, El-Gamal, MI, Abdel-Maksoud, MS, Lee, H, Choi, J, Kim, TW, Shin, JS, Lee, HH, Kim, HK, Lee, KT & Baek, D 2020, 'Inhibitory effects of triarylpyrazole derivatives on LPS-induced nitric oxide and PGE₂ productions in murine RAW 264.7 macrophages', Bioorganic and Medicinal Chemistry Letters, vol. 30, no. 4, 126884. https://doi.org/10.1016/j.bmcl.2019.126884

Inhibitory effects of triarylpyrazole derivatives on LPS-induced nitric oxide and PGE₂ productions in murine RAW 264.7 macrophages. / Gamal El-Din, Mahmoud M.; El-Gamal, Mohammed I.; Abdel-Maksoud, Mohammed S. et al.
In: Bioorganic and Medicinal Chemistry Letters, Vol. 30, No. 4, 126884, 15.02.2020.

Research output: Contribution to journal › Journal article › peer-review

TY - JOUR

T1 - Inhibitory effects of triarylpyrazole derivatives on LPS-induced nitric oxide and PGE2 productions in murine RAW 264.7 macrophages

AU - Gamal El-Din, Mahmoud M.

AU - El-Gamal, Mohammed I.

AU - Abdel-Maksoud, Mohammed S.

AU - Lee, Huijeong

AU - Choi, Jungseung

AU - Kim, Tae Woo

AU - Shin, Ji Sun

AU - Lee, Hwi Ho

AU - Kim, Hee Kwon

AU - Lee, Kyung Tae

AU - Baek, Daejin

PY - 2020/2/15

Y1 - 2020/2/15

N2 - In this article, a series of 22 triarylpyrazole derivatives were evaluated for in vitro antiinflammatory activity as inhibitors of nitric oxide (NO) and prostaglandin E2 (PGE2) release induced by lipopolysaccharide (LPS) in murine RAW 264.7 macrophages. The synthesized compounds 1a-h, 2a-f and 3a-h were first examined for their cytotoxicity for determination of the non-toxic concentration for antiinflammatory screening, so that the inhibitory effects against NO and PGE2 production were not caused by non-specific cytotoxicity. Compounds 1h and 2f were the most active PGE2 inhibitors with IC50 values of 2.94 μM and 4.21 μM, respectively. Western blotting and cell-free COX-2 screening revealed that their effects were due to inhibition of COX-2 protein expression. Moreover, compound 1h exerted strong inhibitory effect on the expression of COX-2 mRNA in LPS-induced murine RAW 264.7 macrophages.

AB - In this article, a series of 22 triarylpyrazole derivatives were evaluated for in vitro antiinflammatory activity as inhibitors of nitric oxide (NO) and prostaglandin E2 (PGE2) release induced by lipopolysaccharide (LPS) in murine RAW 264.7 macrophages. The synthesized compounds 1a-h, 2a-f and 3a-h were first examined for their cytotoxicity for determination of the non-toxic concentration for antiinflammatory screening, so that the inhibitory effects against NO and PGE2 production were not caused by non-specific cytotoxicity. Compounds 1h and 2f were the most active PGE2 inhibitors with IC50 values of 2.94 μM and 4.21 μM, respectively. Western blotting and cell-free COX-2 screening revealed that their effects were due to inhibition of COX-2 protein expression. Moreover, compound 1h exerted strong inhibitory effect on the expression of COX-2 mRNA in LPS-induced murine RAW 264.7 macrophages.

KW - Amide

KW - Antiinflammatory

KW - COX-2

KW - iNOS

KW - NO

KW - PGE

KW - Triarylpyrazole

KW - Urea

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DO - 10.1016/j.bmcl.2019.126884

M3 - Journal article

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AN - SCOPUS:85077151709

SN - 0960-894X

VL - 30

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 4

M1 - 126884

ER -