2. Academic Validation
  3. Bioactivity Study of Tricyclic and Tetracyclic Genipin Derivatives as Anti-inflammatory Agents

Bioactivity Study of Tricyclic and Tetracyclic Genipin Derivatives as Anti-inflammatory Agents

  • Bioorg Chem. 2022 Sep;126:105881. doi: 10.1016/j.bioorg.2022.105881.
Sin-Min Li 1,  Chia-Yin Chiang 2,  Wei-Zheng Zeng 3,  Cheng-Yen Chung 4,  Ching-Chun Tseng 2,  Yu-Pei Hu 5,  Yu-Ching Lin 5,  Guan-Jhong Huang 6,  Ichiro Arai 7,  Der-Yen Lee 8,  Shuo-En Tsai 2,  Fung Fuh Wong 9
Affiliations

Affiliations

  • 1 Institute of New Drug Development, China Medical University, No. 91, Hsueh-Shih Rd., Taichung 40402, Taiwan.
  • 2 Program for Biotech Pharmaceutical Industry, China Medical University, No. 91, Hsueh-Shih Rd., Taichung 40402, Taiwan.
  • 3 Master Program for Pharmaceutical Manufacture, China Medical University, No. 91, Hsueh-Shih Rd., Taichung 40402, Taiwan.
  • 4 Program for Biotech Pharmaceutical Industry, China Medical University, No. 91, Hsueh-Shih Rd., Taichung 40402, Taiwan; Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, China Medical University, No. 91, Hsueh-Shih Rd., Taichung 40402, Taiwan.
  • 5 Department of Biological Science and Technology, China Medical University, Taichung, Taiwan.
  • 6 Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, China Medical University, No. 91, Hsueh-Shih Rd., Taichung 40402, Taiwan; Department of Health and Nutrition Biotechnology, Asia University, Taichung 413, Taiwan.
  • 7 Department of Pharmaceutical Science, Nihon Pharmaceutical University, 10281, Komuro, Inamachi, Kita-Adachigun, Saitama, Japan.
  • 8 Graduate Institute of Integrated Medicine, College of Chinese Medicine, China Medical University, Taichung City 40402, Taiwan.
  • 9 Program for Biotech Pharmaceutical Industry, China Medical University, No. 91, Hsueh-Shih Rd., Taichung 40402, Taiwan; School of Pharmacy, China Medical University, No. 91, Hsueh-Shih Rd., Taichung 40402, Taiwan. Electronic address: [email protected].
PMID: 35636127 DOI: 10.1016/j.bioorg.2022.105881
Abstract

A series of genipin derivatives included tricyclic cyclopentaimidazopyridine, cyclopentapyridopyrimidine, octahydrocyclopentapyridodiazepine, and tetracyclic decahydrobenzoimidazocyclopentapyridine were synthesized and developed as anti-inflammatory agents. All of them were tested against NO production in LPS-induced RAW264.7 cells. Based on IC50 data and the SAR study, we found that tricyclic cyclopentaimidazopyridines 3d-f and 7-9 presented the better inhibitory activities (≦ 28.1 μM) in comparison with the reference standard Indomethacin (166 μM). On the other hand, all of them showed inactivity for in vitro cyclooxygenase COX-2 inhibition assays and compounds 8 and 9 possessed the cell toxity. To explore the further anti-inflammatory mechanism, Western blot analysis was carried out. Furthermore, compound 3d shown better bioactivity than Indomethacin. The suppression of NF-κB signal pathway by compound 3d was also determined. To sum-up, compound 3d would be the potential anti-inflammatory lead compound.

Keywords

Anti-inflammation; Cyclopentaimidazopyridine; Cyclopentapyridopyrimidine; Genipin; Iridoids.

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