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14.sinteza Ac Ursolic
14.sinteza Ac Ursolic
Ursolic acid is a natural compound, a pentacyclic triterpene, found in abundance in many species of native
wild flora. The experimental study was intended to extract ursolic acid from Calluna vulgaris, L. Hull, (Ericaceae)
and its derivatization to obtain dipeptide compounds with potential biological activity. For this purpose, three
dipeptides were used: alanyl-glycine, glycyl-leucine and leucyl-glycine. The biological activity of ursoloilglycyl-leucine has been tested on several cancer cells lines, A2780, A431, HeLa and MCF-7.
Keywords: ursolic acid, dipeptides, biological activity
Experimental part
Ursolic acid was extracted from a dried up mixture of
leaves, flowers and young stems, of Calluna vulgaris, L.
Hull, (Ericaceae), through maceration, for 6 days, at 22C,
using as solvent an ethanol-water solution. All plant
materials were harvested from the Bioara and Ciucea
areas, Cluj County, sorted and oven-dried at 65C for 3 days.
The dried vegetal material was next grinded and the
heterogeneous granular mixture was separated into
granulometric classes. The extraction evolution was
surveyed through refractometry, the influence of various
parameters upon the extraction of the ursolic acid from
the vegetal mass being analyzed. Within the study, there
were used several concentration values of the ethanolwater solution, 30, 50, 60, 70, 80 and 95 %, various
granulometric fractions, + 1250, - 1250, + 125, + 90 and 90 m and different liquid-solid shares, 10 : 1; 20 : 1; 30 : 1
and 40 : 1, (mL : g).
During the experimental study, both the qualitative and
quantitative analysis of the ursolic acid in the extract were
performed through reversed phase high performance liquid
chromatography, (RP-HPLC). The chromatographic
separation was carried out on a column C18, (250 4.6
mm, 5 m), the used mobile phase being represented by a
mixture of acetonitrile and ultra pure water at a ratio of 90
: 10 (v : v) and a flow rate of 0.8 mL / min. Detection was
reached at a wave length of 210 nm.
The dipeptide derivatives were obtained by condensing
the ursolic acid with alanyl-glycine, glycyl-leucine and
leucyl-glycine as showed in figure 2. The synthesis of the
ursolic derivatives occurred over a series of reactions
developed on four successive stages, among which the
first two, corresponding to the obtaining of the intermediary
products, (1a) and (2a), are similar in the research
methodology to those corresponding to the obtaining of
the ursolic derivatives, (4), (6) and (8).
The first reaction was the treatment of ursolic acid with
acetic anhydride resulting in monoacetyl ursolic acid, (1a),
to which, during the second stage, thionyl chloride was
added and the monoacetyl ursolic acid chloride was
obtained, (2a). A quantity of 50 mg ursolic acid was
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Table 1
CHARACTERIZATION OF THE SYNTHESIS
COMPOUNDS (4), (6) AND (8)
Table 2
ANTIPROLIFERATION EFFECT
OF URSOLIC ACID, [23-26], AND
ITS DERIVATIVE URSOLOILGLYCYL-LEUCINE,(6)
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Manuscript received: 12.07.2013
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