A new pyrazolo4,3-i/pyriinidine derivative-. Synthesis and anti-inflammatory activity
10.3969/j.issn.1001-1978.2021.02.016
- Author:
Pei-Jing YU
1
;
Pei-Jing YU
2
;
Yang-Sheng HU
3
;
Liu-Zeng CHEN
3
;
Jing-Bo SHI
3
;
Xin-Hua LIU
3
Author Information
1. Dept of Pharmacy, the First Affiliated Hospital
2. Grade 3 Pharmaceutical Chemistry Lab of State Administration of Traditional Chinese Medicine
3. School of Pharmacy, Anhui Medical University
- Publication Type:Journal Article
- Keywords:
Anti-inflammation;
COX-2;
NF-KB;
NLRP3;
Pyrazolo[4,3-d] pyrimidine;
RAW264. 7
- From:
Chinese Pharmacological Bulletin
2021;37(2):233-239
- CountryChina
- Language:Chinese
-
Abstract:
Aim To design and synthesizea new pyrazolo[4,3-d] pyrimidine derivative for the purpose of developing novel anti-inflammatory agents, and to revealthe possible anti-inflammatory mechanisms of thenew compound using preliminary studies. Methods The changes of the cell morphology were investigated via the microscope. The influence of title compound on the NO production of the L P S - stimulated RAW264. 7 cells was measured by Griess assay. The gene relative transcription levels of TNF-a, IL - 6 and IL-lß were evaluated by qRT-PCR. COX-2 expression was measured by qRT-PCR and western blot. NF-KB/NLRP3 inflammasome signaling pathway were investigated by Western blot. The changes of lung tissue were observed by HE staining in vivo experiments of mice. Results Preliminary mechanism researches revealed that the ti - tle compound could inhibit nitric oxide (NO) generation as well as the expression of COX-2, TNF-a, IL - 6, and IL - lβ by NF-KB/NLRP3 inflammasome signaling pathway in RAW264. 7 cells. Furthermore, it could simultaneously improve the morphology of the cells and relieve acute lung injury in mice. Conclusions The new pyrazolo [4, 3-α] pyrimidine derivative has anti-inflammatory activity through NF-KB/NLRP3 inflammasome signaling pathway.
