ISSN print edition: 0366-6352 ISSN electronic edition: 1336-9075 Registr. No.: MK SR 9/7 Published monthly

Discovery of pyrazole derivatives as potent inhibitor of NF-ĸB for possible benefit in abdominal aortic aneurysms

Yun Guo, Dongming Bao, and Chaogang Zhang

Department of Interventional, Qionglai Medical Center Hospital, Qionglai, China

E-mail: 17358507362m@sina.cn

Received: 17 December 2020  Accepted: 18 May 2021

Abstract:

Numerous 3-(4-substitutedyphenyl)-5-methyl-1-phenyl-1H-pyrazole-4-carboxylate derivatives have been synthesized using H₂SO₄.SiO₂ as a catalyst. These derivatives were subsequently screened for NF-ĸB transcription inhibitory activity in RAW264.7 cells, where they showed mild to significant inhibition. Among the tested derivatives, Compound 4e was identified as a most potent NF-ĸB transcription inhibitor. The effect of compound 4e was further studied in abdominal aortic aneurysm (AAA) animal model in BALB/c mice. The AAA was induced in mice by sub-cuteneous administration of Angiotensin-II (Ang-II). Results suggest that compound 4e significantly inhibited inflammation and oxidative stress in AAA mice as compared to disease control. It also inhibits NF-ĸB and COX-2 in AAA mice as shown by western blot analysis. Collectively, it was concluded that, compound 4e might acts as protective agent against AAA.

Keywords: Pyrazole; One-pot synthesis; Silica; NF-ĸb; COX-2

Full paper is available at www.springerlink.com.

DOI: 10.1007/s11696-021-01707-7

Chemical Papers 75 (9) 4917–4925 (2021)