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

• Published in: Bioorganic & medicinal chemistry letters 2020-02, Vol.30 (4), p.126884, Article 126884
• Main Authors: Gamal El-Din, Mahmoud M., El-Gamal, Mohammed I., Abdel-Maksoud, Mohammed S., Lee, Huijeong, Choi, Jungseung, Kim, Tae-Woo, Shin, Ji-Sun, Lee, Hwi-Ho, Kim, Hee-Kwon, Lee, Kyung-Tae, Baek, Daejin
• Format: Article
• Language: English
• Subjects: Amide; Antiinflammatory; COX-2; iNOS; PGE2; Triarylpyrazole; Urea
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2019.126884

[Display omitted] 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.