Advances in the Study of Structural Modification and Biological Activities of Ursolic Acid

doi:10.6023/cjoc202102032

Abstract

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

Cite this article

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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Fig. & Tab. 12

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

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]

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

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]

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

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

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

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

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

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

Figure 9. Structures of ursolic acid derivatives with antimicrobial activity

Figure 10. Structures of ursolic acid derivatives for neurodegenerative diseases

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