2. Academic Validation
  3. Design, Synthesis, anti-inflammatory activity Evaluation, preliminary exploration of the Mechanism, molecule Docking, and structure-activity relationship analysis of batatasin III analogs

Design, Synthesis, anti-inflammatory activity Evaluation, preliminary exploration of the Mechanism, molecule Docking, and structure-activity relationship analysis of batatasin III analogs

  • Bioorg Med Chem Lett. 2023 Oct 16:96:129527. doi: 10.1016/j.bmcl.2023.129527.
Mingcai Lei 1,  Hanfei Liu 2,  Xin Tan 3,  Chao Chen 4,  Huayong Lou 2,  Mei Zhou 2,  Jinyu Li 2,  Wei Wu 5,  Weidong Pan 6
Affiliations

Affiliations

  • 1 College of Pharmacy, Guizhou University, Guiyang 550014, China.
  • 2 The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences, Guiyang 550014, China.
  • 3 College of Pharmacy, Guizhou Medical University, Guiyang 550014, China.
  • 4 The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences, Guiyang 550014, China; Center for Research and Development of Fine Chemicals, Guizhou University, Guiyang 550014, China.
  • 5 The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences, Guiyang 550014, China. Electronic address: [email protected].
  • 6 College of Pharmacy, Guizhou University, Guiyang 550014, China; The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences, Guiyang 550014, China. Electronic address: [email protected].
PMID: 37852423 DOI: 10.1016/j.bmcl.2023.129527
Abstract

Most clinical drugs used to treat inflammation have serious gastrointestinal, renal, and cardiovascular side effects during long-term treatment. The development of new anti-inflammatory agents from Natural Products and their derivatives is a powerful approach to overcome these adverse effects. Batatasin III, a bibenzyl natural product, has been found to have anti-inflammatory activity. Compared with other anti-inflammatory agents, batatasin III has a simple and unique structure. Therefore, batatasin III and its analogs might have the potential to treat inflammation with only mild adverse effects as a new type of anti-inflammatory agent. Herein, we synthesized 26 batatasin III analogs and evaluated the anti-inflammatory activity in vitro. Analog 21 significantly inhibited (p < 0.01) nitric oxide production with an IC50 value of 12.95 μM. Western blot analysis further revealed that 21 reduced iNOS, phosphorylated p65, and β-catenin expression in a concentration-dependent manner. These results indicated that 21 could be a potential lead compound for developing a drug candidate for ulcerative colitis. Molecular docking analysis showed that p65 might be a potential target of 21 for the treatment of inflammatory disease. In addition, we analyzed the structure-activity relationship of the analogs, which provides a basis for future structural modifications.

Keywords

Batatasin III; INOS; Importin α3; Inflammation; P65; β-catenin.

Figures
Products