Pentacyclic triterpenes ursolic acid

The studies with a goal to explore the variability of biological responses from the perspective of sample purity have been performed by Jaki et al For this purpose nine different samples of the pentacyclic plant triterpene ursolic acid with purity certifications were obtained, and their purity was independently assessed by means of quantitative HNMR. Biological evaluation consisted of determining MICs against two strains of virulent Mycobacterium tuberculosis and IC50 values in Vero cells. Ab initio structure elucidation provided unequivocal structural confirmation and included an extensive H NMR spin system analysis, determination of nearly all /hh couplings and the complete NOE pattern, which led to a revision of earlier reports. 

The betulinic acid level in the E. florida leaves increased significantly in the May, June, Jully (autumn - winter) and, September, October and November (winter) which was mainly due to the accumulation of this compound in vegetal tissue. Some authors related with the pentacyclic triterpenes, just as betulinic, acid ursolic, acid, p-amyrine and lupeol, are supposed to be toxic to insects, due to their ability to inhibit acyl chain packing in the lipid bilayers of the insect membranes [Rodriguez et al, 1997 Prades et al., 2011]. 

Triterpenic Acids. The following pentacyclic mono- and dihydroxy triterpenic acids are present in virgin olive oil (35, 43, 44) 3p-hydroxy-17-carboxy-5-12-olea-nene (oleanolic acid) 3 3,2a-dihydroxy-17-carboxy-5-12-oleanene (maslinic acid) 3p-hydroxy-17-carboxy-8-12-ursene (ursolic acid) 2a,3p-dihydroxy-17-carboxy-5-12-ursene (2a-hydroxyursolic acid) and deoxyursolic acid (structure not fully elucidated). 

The boswellic acid derivative, AKBA, decreases the activity of HLE in vitro in a concentration-dependent manner, with an IC50 value of 15 iM. This result has been compared with those obtained with ursolic acid, amyrin and 18p-glycyrrhetinic acid, the last of which showed no inhibitory activity on HLE at concentrations up to 20 pM [105]. Data analyses indicate different mechanisms for the inhibitory actions of the pentacyclic triterpenes AKBA and ursolic acid inhibition is noncompetitive in the case of AKBA but competitive with ursolic acid. These results are in line with the hypothesis that pentacyclic triterpenes interact with the extended substrate-binding domain in HLE that can bind a variety of hydrophobic ligands [104]. Depending on the substrate length, HLE inhibition can be competitive (ursolic acid) or non-competitive (AKBA). 

Ursane. C30H52, Mr 412.74, see figure under triter-penes. The pentacyclic, saturated triterpene skeleton, substituted by 8 methyl groups, of ursolic acid and a- amyrin. 

In the oleanane-ursane group of triterpenes, postulated hydride shifts [as proposed by Eschenmoser and co-workers (1955)] have now been demonstrated. Incorporation of [4- C]MVA into oleanolic acid (56), ursolic acid (63), and several other metabolites was accomplished with tissue cultures of Isodon japonicus (Lamiaceae). Following introduction of [4- C]mevalonate and [l,2- C2]acetate, the pentacyclic triterpene compounds were examined by C-NMR spectroscopy. Rings D and E were formed by the routes predicted by Eschenmoser et al. (1955). The labeling pattern at carbons 4,23, and 24 of 3- p/-maslinic acid (64) indicates that this series is formed from (35)-squalene epoxide, rather than from the (3R)-epimer. 

Most of the 20 odd triterpenes that have been structurally determined are derived from pentacyclic hopane (94). The exceptions are friedelin (95), epifriedelanol, taraxerene, ursolic acid, and diacetyl pyxinol. 

C. officinalis Sieb (Comaceae) is used traditionally as a tonic. The antidiabetic activity of this plant has been reported in streptozotocin-induced diabetic rats when given per os [112]. Ursolic acid (0.14%), a pentacyclic triterpene acid, caused about 30% of reduction on blood glucose levels when administered for 6 weeks in high-fat diet mice [113], The main underlying mechanism of action seems to be mediated by the increase of the insulin-sensitive glucose... 

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