Evaluation of the Inhibitory Effects of Pyridylpyrazole Derivatives on LPS-Induced PGE<sub>2</sub> Productions and Nitric Oxide in Murine RAW 264.7 Macrophages
Mahmoud M. Gamal El-Din,
Mohammed I. El-Gamal,
Young-Do Kwon,
Su-Yeon Kim,
Hee-Soo Han,
Sang-Eun Park,
Chang-Hyun Oh,
Kyung-Tae Lee,
Hee-Kwon Kim
Affiliations
Mahmoud M. Gamal El-Din
National Research Centre, Pharmaceutical and Drug Industries Research Division, Dokki-Giza 12622, Egypt
Mohammed I. El-Gamal
Department of Medicinal Chemistry, College of Pharmacy, University of Sharjah, Sharjah 27272, United Arab Emirates
Young-Do Kwon
Molecular Imaging & Therapeutic Medicine Research Center, Department of Nuclear Medicine, Jeonbuk National University Medical School and Hospital, 20 Geonji-ro, Deokjin-gu, Jeonju 54907, Korea
Su-Yeon Kim
Department of Pharmaceutical Biochemistry, Kyung Hee University, Seoul 02447, Korea
Hee-Soo Han
Department of Pharmaceutical Biochemistry, Kyung Hee University, Seoul 02447, Korea
Sang-Eun Park
Department of Pharmaceutical Biochemistry, Kyung Hee University, Seoul 02447, Korea
Chang-Hyun Oh
Center for Biomaterials, Korea Institute of Science and Technology, P.O. Box 131, Cheongryang, Seoul 130-650, Korea
Kyung-Tae Lee
Department of Pharmaceutical Biochemistry, Kyung Hee University, Seoul 02447, Korea
Hee-Kwon Kim
Molecular Imaging & Therapeutic Medicine Research Center, Department of Nuclear Medicine, Jeonbuk National University Medical School and Hospital, 20 Geonji-ro, Deokjin-gu, Jeonju 54907, Korea
A series of thirteen triarylpyrazole analogs were investigated as inhibitors of lipopolysaccharide (LPS)-induced prostaglandin E2 (PGE2) and nitric oxide (NO) production in RAW 264.7 macrophages. The target compounds 1a–m have first been assessed for cytotoxicity against RAW 264.7 macrophages to determine their non-cytotoxic concentration(s) for anti-inflammatory testing to make sure that the inhibition of PGE2 and NO production would not be caused by cytotoxicity. It was found that compounds 1f and 1m were the most potent PGE2 inhibitors with IC50 values of 7.1 and 1.1 μM, respectively. In addition, these compounds also showed inhibitory effects of 11.6% and 37.19% on LPS-induced NO production, respectively. The western blots analysis of COX-2 and iNOS showed that the PGE2 and NO inhibitory effect of compound 1m are attributed to inhibition of COX-2 and iNOS protein expression through inactivation of p38.
