熊果酸的结构修饰与生物活性研究进展

doi:10.6023/cjoc202102032

摘要/Abstract

熊果酸是从药用植物、水果和蔬菜中提取的具有多种药理活性的五环三萜类化合物. 近年来, 熊果酸的药理作用得到了广泛的研究, 大量研究表明熊果酸具有多种药理活性, 包括抗癌、抗炎、抗氧化、抗菌、抗糖尿病等. 熊果酸虽然具有广泛的生物学活性, 但其水溶性差、生物利用度低等限制了在临床上的应用. 为了克服这些缺点, 国内外研究人员通过对熊果酸母体骨架进行化学修饰, 设计并开发了大量结构新颖、活性强的熊果酸衍生物. 对近年来合成的有进一步研究价值的熊果酸衍生物及其生物活性研究进展进行总结, 为以熊果酸为先导化合物的药物研究提供参考.

关键词: 熊果酸, 结构修饰, 抗肿瘤, 抗糖尿病, 抗炎, 抗菌

Ursolic acid (UA) belongs to a group of pentacyclic triterpenoids extracted from medicinal plants, fruits and vegetables. In recent years, the pharmacological action of ursolic acid has been widely studied. It has been reported that UA has a variety of pharmacological activities, including anti-cancer, anti-inflammation, anti-oxidation, anti-bacterial, anti-diabetes and so on. In spite of that UA shows the extensive therapeutic potential as a drug candidate, the poor water solubility and low bioavailability of UA limit its clinical application. To address these issue, large numbers of UA-based derivatives with enhanced activities and better physicochemical character have been developed by structural modification of its parent skeleton. In this paper, the research progress of the synthesized UA derivatives with therapeutic potential along with their biological activities is reviewed, which provides reference for further drug development using UA as a lead compound.

Key words: ursolic acid, structural modification, anti-tumor, anti-diabetic, anti-inflammatory, antiviral

引用此文

刘改枝, 李金鑫, 史礼君, 刘萌芽, 蔡邦荣. 熊果酸的结构修饰与生物活性研究进展[J]. 有机化学, 2021, 41(8): 2974-2989.

Gaizhi Liu, Jinxin Li, Lijun Shi, Mengya Liu, Bangrong Cai. Advances in the Study of Structural Modification and Biological Activities of Ursolic Acid[J]. Chinese Journal of Organic Chemistry, 2021, 41(8): 2974-2989.

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图/表 12

图1. 熊果酸的结构及其主要修饰位点

Figure 1. Structure of ursolic acid and its major modification sites

图2. 熊果酸C-3位修饰衍生物的结构

Figure 2. Structures of ursolic acid C-3 modified derivatives

Compd.	Ref.	Compd.	R	Ref.
10	[11]	17		[14]
11	[12]	18		[14]
12	[12]	19		[15, 16]
13	[13]	20		[17]
14	[14]	21		[18]
15	[14]	22		[19]
16	[14]	23	CH(CH₃)₂	[10]

表1. 熊果酸C-28位修饰衍生物的结构

Table 1. Structures of ursolic acid derivatives modified at C-28

图3. 部分C-28位修饰熊果酸衍生物的结构

Figure 3. Structures of ursolic acid derivatives modified at C-28

Compd.	R¹	R²	Ref.	Compd.	R¹	R²	Ref.
27	OAc		[23]	36	OMe		[32]
28	OAc		[24]	37	OMe	N(CH₂CH₂OH)₂	[32]
29	OAc		[25]	38	OMe		[32]
30	OAc		[26]	39	OMe		[32]
31	OAc		[27]	40			[33]
32	OAc	NH(CH₂)₆NH₂	[28]	41			[33]
33	OAc	NHOH; N(CH₃)OH	[29]	42			[34]
34	OAc		[30]	43	=O		[35]
35	OAc		[31]	44	COOC₃H₇		[36]

表2. 熊果酸C-3, C-28位同时修饰衍生物的结构

Table 2. Simultaneous modification of C-3, C-28 sites of ursolic acid derivatives

图4. 孟艳秋课题组合成的部分C-3位和C-28位同时修饰的熊果酸衍生物结构

Figure 4. Structures of ursolic acid derivatives modified simultaneously at C-3 and C-28 sites by Meng yanqiu group

图5. A环及其他位点修饰的熊果酸衍生物的结构

Figure 5. Structures of ursolic acid derivatives modified by A ring and other sites

图6. 具有抗糖尿病和心血管疾病活性的熊果酸衍生物结构

Figure 6. Structures of ursolic acid derivatives with anti-diabetes activity and anti-cardiovascular activity

图7. 具有抗炎活性的熊果酸衍生物的结构

Figure 7. Structures of ursolic acid derivatives with anti-inflammatory activity

图8. 具有预防骨损伤活性的熊果酸衍生物的结构

Figure 8. Structure of ursolic acid derivatives with bone protective activity

图9. 具有抗病原微生物活性的熊果酸衍生物的结构

Figure 9. Structures of ursolic acid derivatives with antimicrobial activity

图10. 具有抗神经系统疾病活性的熊果酸衍生物的结构

Figure 10. Structures of ursolic acid derivatives for neurodegenerative diseases

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