三类基于香豆素母核衍生物的合成及其抗炎活性

赵秀娟; 杨恒俐; 吴金叶; 郑晓琦; 张耀苹; 林玉萍; 虎春艳

doi:10.11665/j.issn.1000-5048.2024072101

三类基于香豆素母核衍生物的合成及其抗炎活性

云南中医药大学中药学院, 昆明 650500

基金项目: 云南省科学技术厅-云南中医药大学应用基础研究联合专项资助项目（202301AZ070001-061）

详细信息

通讯作者:
虎春艳: Tel：13078754255　E-mail：hchuny@126.com

中图分类号: R914；R965
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出版历程
- 收稿日期: 2024-07-20
- 修回日期: 2024-08-26
- 录用日期: 2024-09-08
- 刊出日期: 2025-02-24

Synthesis and anti-inflammatory activity of three series of coumarin-based derivatives

College of Traditional Chinese Medicine, Yunnan University of Chinese Medicine, Kunming 650500, China

Funds: This study was supported by the Applied Basic Research Joint Special Funds of Yunnan Provincial Science and Technology Department and Yunnan University of Chinese Medicine（202301AZ070001-061)

摘要

摘要:
以4-羟基香豆素为原料出发，合成得到3个系列共22个香豆素衍生物，其中8个衍生物未见文献报道，并采用小鼠巨噬细胞模型对其体外抗炎活性及作用机制进行初步研究。结果表明，大部分衍生物均可显著抑制促炎因子NO的生成，其中化合物2e、2f、2g、2h、2i、2j、4e和4f的抗炎活性优于阳性对照药物地塞米松。进一步实验发现，化合物2h和4f可显著抑制RAW264. 7巨噬细胞内促炎因子IL-6、TNF-α和IL-1β的生成，可作为先导化合物进行深入研究。
- 香豆素衍生物 /
- 合成 /
- 抗炎活性
Abstract:
In this work, starting from 4-hydroxycoumarin, three series of 22 coumarin derivatives, among which 8 have not been reported in the literature, were synthesized and their in vitro anti-inflammatory activities and mechanisms of action were preliminarily investigated using mouse macrophage model. The results showed that most of the derivatives could significantly inhibit the production of pro-inflammatory factor NO, with compounds 2e, 2f, 2g, 2h, 2i, 2j, 4e, and 4f showing better anti-inflammatory activity than the positive control drug dexamethasone. Further experiments showed that compounds 2h and 4f significantly inhibited the production of pro-inflammatory factors IL-6, TNF-α and IL-1β in RAW264.7 macrophages, and could, therefore, be used as lead compounds for further studies.
- coumarin derivatives /
- synthesis /
- anti-inflammatory activity

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1. Synthesis of coumarin-based derivatives

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Figure 1. Inhibitory effect of compounds on LPS-induced NO expression in RAW264.7 cells ($\bar{x}\pm s$, n= 3)

CON：Control；LPS: Lipopolysaccharide; DEX:Dexamethasone ^### P<0.001 vs control group；^*** P<0.001 vs LPS group

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Figure 2. Inhibition of compounds 2h and 4f on LPS-induced pro-inflammatory factors IL-6 (A), TNF-α (B) and IL-1β (C) in RAW264.7 cells detected by ELISA ($\bar{x}\pm s $, n= 3)

RAW264.7 cells were treated with compounds 2h and 4f (5, 10, and 20 μmol/L) for 2 h, and then with LPS for 24 h ^### P<0.001 vs control group； ^* P<0.05，^** P<0.01, ^*** P<0.001 vs LPS group

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Table 1 Structure and inhibitory of coumarin-based derivatives (20 μmol/L) on RAW264.7

Compd.	R	Yields /%	Cell viability /%	Compd.	R	Yields /%	Cell viability/%
2a		88.5	43.7	3a		78.8	49.9
2b		86.7	42.4	3b		71.2	45.2
2c		90.5	48.9	3c		49.8	40.0
2d		85.8	45.8	3d		49.0	39.5
2e		86.4	84.8	3e		59.8	43.4
2f		87.9	51.8	4a		61.6	34.0
2g		91.2	57.9	4b		64.3	34.2
2h		87.4	97.5	4c		66.1	49.8
2i		87.9	83.1	4d		76.9	49.8
2j		85.6	63.0	4e		70.5	65.3
2k		87.4	36.9	4f		84.1	98.5

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Table 2 In vitro anti-inflammatory activity of coumarin derivatives

Compd.	NO generation (IC₅₀, μmol/L)	Compd.	NO generation (IC₅₀, μmol/L)
2e	11.32 ± 1.02	2i	7.92 ± 0.32
2f	8.22 ± 0.74	2j	9.09 ± 0.44
2g	9.42 ± 1.52	4e	12.16 ± 0.43
2h	6.76 ± 0.22	4f	5.49 ± 0.44

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