2. Academic Validation
  3. Design, synthesis, and SAR study of novel flavone 1,2,4-oxadiazole derivatives with anti-inflammatory activities for the treatment of Parkinson's disease

Design, synthesis, and SAR study of novel flavone 1,2,4-oxadiazole derivatives with anti-inflammatory activities for the treatment of Parkinson's disease

  • Eur J Med Chem. 2023 Apr 28;255:115417. doi: 10.1016/j.ejmech.2023.115417.
Zhen-Bao Shen 1,  Hua-Wen Meng 1,  Xian-She Meng 1,  Ze-Kun Lv 1,  Meng-Yuan Fang 1,  Lang-Lang Zhang 1,  Zhi-Lin Lv 1,  Mu-Sen Li 1,  An-Kang Liu 1,  Ji-Hong Han 1,  Qing-Shan Li 2,  Ya-Jun Duan 3
Affiliations

Affiliations

  • 1 Key Laboratory of Metabolism and Regulation for Major Diseases of Anhui Higher Education Institutes, College of Food and Biological Engineering, Hefei University of Technology, Hefei, China.
  • 2 Key Laboratory of Metabolism and Regulation for Major Diseases of Anhui Higher Education Institutes, College of Food and Biological Engineering, Hefei University of Technology, Hefei, China. Electronic address: liqs@hfut.edu.cn.
  • 3 Key Laboratory of Metabolism and Regulation for Major Diseases of Anhui Higher Education Institutes, College of Food and Biological Engineering, Hefei University of Technology, Hefei, China; Department of Cardiology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China. Electronic address: yajunduan@ustc.edu.cn.
PMID: 37137246 DOI: 10.1016/j.ejmech.2023.115417
Abstract

Inflammation is one of a major feature of Parkinson's disease (PD) which poses a threat to people's health in the world. It has been reported that antioxidation and anti-inflammation have significant effects on the treatment of PD. 1,2,4-oxadiazole and flavone derivatives have remarkable antioxidant and anti-inflammatory activities. In order to find highly effective drugs for PD treatment, based on the remarkable anti-inflammatory and antioxidant activities of the 1,2,4-oxadiazole pharmacophore and the flavonoid pharmacophore, we designed and synthesized a novel series of 3-methyl-8-(3-methyl-1,2,4-oxadiazol-5-yl)-2-phenyl-4H-chromen-4-one derivatives by pharmacophore combination, and evaluated their anti-inflammatory and antioxidation activities for PD treatment. Preliminary structure-activity relationship (SAR) analysis was conducted by their inhibitory activities against Reactive Oxygen Species (ROS) and NO release in LPS-induced BV2 Microglia cells, and the optimal compound Flo8 exhibited the most potent anti-inflammatory and antioxidant activities. Both in vivo and in vitro results showed that Flo8 inhibited neuronal Apoptosis by inhibiting inflammatory and apoptotic signaling pathways. In vivo studies also showed that the compound Flo8 ameliorated motor and behavioral deficits and increased serum dopamine levels in MPTP-induced PD model mice. Taken together, this study demonstrated the compound Flo8 could be a promising agent for the treatment of PD.

Keywords

1,2,4-oxadiazole; Anti-inflammatory Agent; Flavone; Inflammation; Parkinson's disease.

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