Synthesis of lathyrane diterpenoid nitrogen-containing heterocyclic derivatives and evaluation of their anti-inflammatory activities. (15th February 2022)

• Record Type: Journal Article
• Authors: Wang, Wang; Xiong, Liangliang; Li, Yutong; Song, Zhuorui; Sun, Dejuan; Li, Hua; Chen, Lixia
• Is Part Of: Bioorganic & medicinal chemistry. Volume 56(2022)
• Publication Date: 2022-02-15
• Subjects: Lathyrane -- Pyrazole -- Thiazole -- Furoxan -- Anti-inflammation -- Structural modification; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2022.116627
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: Highlights: Three series of lathyrane diterpenoid derivatives with introduction of nitrogen-containing heterocyclic moieties were synthesized. Among all derivatives, 23d showed the strongest anti-inflammatory activity on RAW264.7 cells. 23d could inhibit Nrf2/HO-1 signaling pathway. 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.