2. Academic Validation
  3. Synthesis of lathyrane diterpenoid nitrogen-containing heterocyclic derivatives and evaluation of their anti-inflammatory activities

Synthesis of lathyrane diterpenoid nitrogen-containing heterocyclic derivatives and evaluation of their anti-inflammatory activities

  • Bioorg Med Chem. 2022 Feb 15;56:116627. doi: 10.1016/j.bmc.2022.116627.
Wang Wang 1,  Liangliang Xiong 1,  Yutong Li 1,  Zhuorui Song 1,  Dejuan Sun 2,  Hua Li 3,  Lixia Chen 4
Affiliations

Affiliations

  • 1 Wuya College of Innovation, Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, China.
  • 2 Wuya College of Innovation, Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, China. Electronic address: sywysdj@163.com.
  • 3 Wuya College of Innovation, Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, China; Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. Electronic address: li_hua@hust.edu.cn.
  • 4 Wuya College of Innovation, Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, China. Electronic address: syzyclx@163.com.
PMID: 35063896 DOI: 10.1016/j.bmc.2022.116627
Abstract

As our ongoing work on lathyrane diterpenoid derivatization, three series of lathyrane diterpenoid derivatives were designed and synthesized based combination principles, including pyrazole, thiazole and furoxan moieties. Biological evaluation indicated that compound 23d exhibited excellently inhibitory activity on LPS-induced NO production in RAW264.7 cells (IC50 = 0.38 ± 0.18 μM). The preliminary structure-activity relationships (SARs) suggested that phenylsulfonyl substituted furoxan moiety had the strongest ability to improve anti-inflammatory activity of lathyrane Diterpenoids. Furthermore, compound 23d significantly reduced the level of ROS. Its molecular mechanism was related to inhibiting the transcriptional activation of Nrf2/HO-1 pathway. Based on these considerations, 23d might be a promising anti-inflammatory agent, which is noteworthy for further exploration.

Keywords

Anti-inflammation; Furoxan; Lathyrane; Pyrazole; Structural modification; Thiazole.

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