Synthesis of New Triarylpyrazole Derivatives Possessing Terminal Sulfonamide Moiety and Their Inhibitory Effects on PGE2 and Nitric Oxide Productions in Lipopolysaccharide-Induced RAW 264.7 Macrophages
Mohammed S. Abdel-Maksoud,
Mohammed I. El-Gamal,
Mahmoud M. Gamal El-Din,
Yunji Choi,
Jungseung Choi,
Ji-Sun Shin,
Shin-Young Kang,
Kyung Ho Yoo,
Kyung-Tae Lee,
Daejin Baek,
Chang-Hyun Oh
Affiliations
Mohammed S. Abdel-Maksoud
Medicinal & Pharmaceutical Chemistry Department, Pharmaceutical and Drug Industries Research Division, National Research Centre (NRC), Dokki, Giza 12622, Egypt
Mohammed I. El-Gamal
Department of Medicinal Chemistry, College of Pharmacy, University of Sharjah, Sharjah 27272, United Arab Emirates
Mahmoud M. Gamal El-Din
Medicinal & Pharmaceutical Chemistry Department, Pharmaceutical and Drug Industries Research Division, National Research Centre (NRC), Dokki, Giza 12622, Egypt
Yunji Choi
Department of Chemistry, Hanseo University, Seosan 31962, Korea
Jungseung Choi
Department of Chemistry, Hanseo University, Seosan 31962, Korea
Ji-Sun Shin
Department of Pharmaceutical Biochemistry, College of Pharmacy, Kyung Hee University, Seoul 02792 Korea
Shin-Young Kang
Department of Pharmaceutical Biochemistry, College of Pharmacy, Kyung Hee University, Seoul 02792 Korea
Kyung Ho Yoo
Department of Chemistry, Hanseo University, Seosan 31962, Korea
Kyung-Tae Lee
Department of Pharmaceutical Biochemistry, College of Pharmacy, Kyung Hee University, Seoul 02792 Korea
Daejin Baek
Department of Chemistry, Hanseo University, Seosan 31962, Korea
Chang-Hyun Oh
Center for Biomaterials, Korea Institute of Science and Technology, Cheongryang, Seoul 130-650, Korea
This article describes the design, synthesis, and in vitro anti-inflammatory screening of new triarylpyrazole derivatives. A total of 34 new compounds were synthesized containing a terminal arylsulfonamide moiety and a different linker between the sulfonamide and pyridine ring at position 4 of the pyrazole ring. All the target compounds were tested for both cytotoxicity and nitric oxide (NO) production inhibition in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages. Compounds 1b, 1d, 1g, 2a, and 2c showed the highest NO inhibition percentages and the lowest cytotoxic effect. The most potent derivatives were tested for their ability to inhibit prostaglandin E2 (PGE2) in LPS-induced RAW 264.7 macrophages. The IC50 for nitric oxide inhibition, PGE2 inhibition, and cell viability were determined. In addition, 1b, 1d, 1g, 2a, and 2c were tested for their inhibitory effect on LPS-induced inducible nitric oxide synthase (iNOS) and Cyclooxygenase 2 (COX-2) protein expression as well as iNOS enzymatic activity.
