However, plant cultures occupy a
large area of cultivated land and plant growth may be affected by
climate change and growth cycle, which subsequently reduces the adequate
supply of raw materials. The challenges for UA’s application also do
include current production methods which consume a lot of organic
reagents, and eventually produce waste liquids to cause serious
ecological pressure to surrounding environment. So the traditional
extractions of UA make it difficult to meet the commercial needs and
environmental protection goals.
Structure modification
to improve the efficacy of UA
Although UA exhibits remarkable physiological and pharmacological
activities with effective and safe therapeutic profile, its poor water
solubility, short plasma half-life and poor bioavailability limit
further clinical applications 44. In this regard,
structural modifications of UA to cope with these limitations have been
an attractive area of research to explore its valuable derivatives with
enhanced pharmacological profile. In recent years, structural
modification of UA is achieved by means of
chemical transformation and
microbial transformation to yield valuable derivatives.
4.1Chemical modification
UA
structure is characterized by a hydroxyl group and carboxylic group
which can be involved in the transfer of lone pair electrons to metal
atoms 45. According to the structural properties of
reported derivatives, UA usually undergoes
structural modifications on
C-3/C-28 positions or the ring A of UA skeleton.
4.1.1Modifications on C-3/C-28
Researchers isolated UA and five triterpenoids from apple peel and
synthesized a series of UA analogs. Structural modification of UA at C-3
indicated significant anti-proliferative activity 46.
In another study, acetyl group at the C-3 and an alkylamino and/or
piperidine moiety at the C-28 enhanced the anticancer activity of UA
derivative 46 (Fig. 2A ). In addition,
structural modification of UA by addition of piperazine moieties may
enhance its anti-cancer properties. Addition of acyl piperazine motif at
C-28 position while C-3 retains the polar group significantly enhanced
the anticancer activity against breast cancer and gastric cancer cell
lines 47 (Fig. 2B ).
In order to clear on the mechanism of chemical modification at C-3 and
C-28 in detail, researchers synthesized a series of UA derivatives by
employing different electronic chemical modification at the two sites.
Derivatives showed stronger cytotoxicity due to presence of positive
charge (Fig. 2C ), indicating that the increased lipophilicity may
enhance the therapeutic potential of gastric carcinoma48. These findings of UA derivatives led the ways to
structurally modify the UA skeleton to yield its valuable derivatives
with diverse pharmacological properties.