Design, Synthesis, and Structure-Activity Relationship Analysis of Thiazolo[3,2-a]pyrimidine Derivatives with Anti-inflammatory Activity in Acute Lung Injury

Autor: Yugui Gu, Siyang Xiao, Chen Feng, Zhiguo Liu, Chenglong Li, Yiyi Jin, Weitao Fu, Bo Fang, Guang Liang, Yunjie Zhao, Lingfeng Chen
Rok vydání: 2017
Předmět:
0301 basic medicine
Lipopolysaccharides
Lipopolysaccharide
Pyrimidine
medicine.drug_class
Acute Lung Injury
Antigens
Differentiation
Myelomonocytic
Quantitative Structure-Activity Relationship
Pharmacology
Lung injury
01 natural sciences
Biochemistry
Anti-inflammatory
03 medical and health sciences
chemistry.chemical_compound
In vivo
Antigens
CD
Sepsis
Drug Discovery
medicine
Structure–activity relationship
Animals
RNA
Messenger
General Pharmacology
Toxicology and Pharmaceutics
Mice
Inbred ICR
010405 organic chemistry
business.industry
Interleukin-6
Tumor Necrosis Factor-alpha
Organic Chemistry
Anti-Inflammatory Agents
Non-Steroidal
Interleukin
Pneumonia
respiratory system
respiratory tract diseases
0104 chemical sciences
Mice
Inbred C57BL
Thiazoles
030104 developmental biology
Pyrimidines
chemistry
Immunology
Macrophages
Peritoneal
Molecular Medicine
Tumor necrosis factor alpha
business
Zdroj: ChemMedChem. 12(13)
ISSN: 1860-7187
Popis: Acute lung injury (ALI) has a high lethality rate, and interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) contribute most to tissue deterioration in cases of ALI. In this study, we designed and synthesized a new series of thiazolo[3,2-a]pyrimidine derivatives based on a previously identified lead compound, and we evaluated their anti-inflammatory activities. Structure-activity relationship studies led to the discovery of two highly potent inhibitors. The two promising compounds were found to inhibit lipopolysaccharide (LPS)-induced IL-6 and TNF-α release in a dose-dependent manner in mouse primary peritoneal macrophages (MPMs). Furthermore, administration of these compounds resulted in lung histopathological improvements and attenuated LPS-induced ALI in vivo. Taken together, these data indicate that these novel thiazolo[3,2-a]pyrimidine derivatives could be developed as candidate drugs for the treatment of ALI.
Databáze: OpenAIRE
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