Antimycobacterial activity of cinnamate-based esters of the triterpenes betulinic, oleanolic and ursolic acids

Betulinic acid, oleanolic acid and ursolic acid have been modified at the C-3 position to cinnamate-based esters and in vitro antimycobacterial activity against Mycobacterium tuberculosis H(37)Ra has been determined. The results indicated that modification of the parent structures of betulinic acid, oleanolic acid and ursolic acid to the p-coumarate and, in the case of the latter two triterpenes, the ferulate ester analogues resulted in high antimycobacterial activity. Structure-activity relationships within the lupane, oleanane and ursane analogues and between these triterpenes are discussed.     

Selective solid-phase extraction of a triterpene acid from a plant extract by molecularly imprinted polymer

A molecularly imprinted polymer (MIP) has been prepared by a thermal polymerisation method using methacrylic acid as functional monomer, ethylene glycol dimethacrylate as cross-linking agent, chloroform as porogenic solvent and an oleanane triterpene compound (18-beta-glycyrrhetinic acid) as imprinted molecule (template). Equilibrium ligand binding experiments were done to assess the performance of the MIP relative to non-imprinted polymer (NIP). After optimisation of SPE protocol (CHCl3 as washing solvent and MeOH as elution solvent), successful imprinting was confirmed by comparison of the recoveries between NIP (5%) and MIP (97%) cartridges. The binding capacity of the MIP for 18-beta-glycyrrhetinic acid was determined to be 0.94 mg g(-1). Four structurally related oleanane triterpenes (18-alpha-glycyrrhetinic acid, oleanolic acid, echinocystic acid, erythrodiol) were selected to assess the MIP selectivity. Experimental data illustrated the influence of functional groups on the triterpene skeleton. The MIP was applied to the solid-phase extraction of triterpenoids from a plant extract prior HPLC analysis. However, CHCl3 was replaced by ACN during the washing step in order to suppress non-specific interactions due to polar matrix components. A selective extraction of 18-beta-glycyrrhetinic acid from hydrolyzed extract of liquorice roots was achieved with a good extraction yield (98%).     

Four new oleanane saponins from Anemone anhuiensis

Four new oleanane triterpene saponins, anhuienosides C-F, together with three known saponins, were isolated from the rhizomes of Anemone anhuiensis (Ranunculaceae). The structures of anhuienosides C-F were elucidated as 3-O-alpha-L-rhamnopyranosyl-(1-->2)-beta-D-xylopyranosyl oleanolic acid 28-O-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranosyl ester, 3-O-beta-D-xylopyranosyl oleanolic acid 28-O-alpha-L-rhamnopyranosyl-(1-->4)-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranosyl ester, 3-O-alpha-L-rhamnopyranosyl-(1-->2)-beta-D-glucopyranosyl oleanolic acid 28-O-alpha-L-rhamnopyranosyl-(1-->4)-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranosyl ester, 3-O-beta-D-glucopyranosyl-(1-->3)-alpha-L-rhamnopyranosyl-(1-->2)-beta-D-xylopyranosyl oleanolic acid 28-O-alpha-L-rhamnopyranosyl-(1-->4)-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranosyl ester, respectively.     

Pentacyclic Triterpene Profile and Its Biosynthetic Pathway in Cecropia telenitida as a Prospective Dietary Supplement

Promising research over the past decades has shown that some types of pentacyclic triterpenes (PTs) are associated with the prevention of type 2 diabetes (T2D), especially those found in foods. The most abundant edible sources of PTs are those belonging to the ursane and oleanane scaffold. The principal finding is that Cecropia telenitida contains abundant oleanane and ursane PT types with similar oxygenation patterns to those found in food matrices. We studied the compositional profile of a rich PT fraction (DE16-R) and carried out a viability test over different cell lines. The biosynthetic pathway connected to the isolated PTs in C. telenitida offers a specific medicinal benefit related to the modulation of T2D. This current study suggests that this plant can assemble isobaric, positional isomers or epimeric PT. Ursane or oleanane scaffolds with the same oxygenation pattern are always shared by the PTs in C. telenitida, as demonstrated by its biosynthetic pathway. Local communities have long used this plant in traditional medicine, and humans have consumed ursane and oleanane PTs in fruits since ancient times, two key points we believe useful in considering the medicinal benefits of C. telenitida and explaining how a group of molecules sharing a closely related scaffold can express effectiveness.     

Simultaneous determination of five triterpene acids in rat plasma by liquid chromatography–mass spectrometry and its application in pharmacokinetic study after oral administration of Folium Eriobotryae effective fraction

Folium Eriobotryae effective fraction (FEA), the extract of Folium Eriobotryae, had been used as anti‐hyperglycemia and anti‐hyperlipemia medicine in China. A previous study indicated that euscaphic acid, maslinic acid, corosolic acid, oleanolic acid and ursolic acid, the five structurally similar triterpene acids (containing two groups of structural isomers), are the major components of FEA. In the present study, we developed a specific and reliable LC‐MS method for simultaneous determination of the five triterpene acids in rat plasma, and further investigated their pharmacokinetic properties after oral administration of FEA. Following a simple sample preparation, chromatographic separation was achieved on a C₁₈ column with a mobile phase composed of methanol–0.1% ammonium acetate (80:20, v/v). Quantification was achieved by monitoring the selected ions at m/z 487.6 for euscaphic acid, m/z 471.5 for maslinic acid and corosolic acid, m/z 455.5 for oleanolic acid and ursolic acid and m/z 469.5 for internal standard. The method was validated to be specific, accurate and precise over the concentration ranges of 10–3000 ng/mL with limits of detections of 5 ng/mL for the five triterpene acids. Finally, the method was successfully applied to the pharmacokinetic study of the five structurally similar triterpene acids in rats after oral administration of FEA. Copyright © 2015 John Wiley & Sons, Ltd.     

Chemical constituents of two sages with free radical scavenging activity

From the aerial parts of Salvia trichoclada Bentham and S. verticillata L. one new and two known phenolic acids, 3-(3',4'-dihydroxyphenyl)-2-hydroxymethyl propionic acid (1), 3-(3',4'-dihydroxyphenyl) lactic acid (2), and rosmarinic acid (3); two flavonoids, apigenin 4'-methyl ether 7-O-glucuronide (4), and luteolin 7-O-beta glucuronide (5); two lupan type triterpene aglycones, lupeol (6), and 30-hydroxylup-20 (29)-en-3-on (7); an oleanane-type triterpene acid, oleanolic acid (8); and an ursan-type triterpene acid, ursolic acid (9) were isolated. The structures of the compounds were elucidated by spectroscopic analysis. Different extracts of the plants were examined for their free radical scavenging activities by DPPH (2,2-Diphenyl-1-picrylhydrazyl) assay. Some of the polar extracts showed high free radical scavenging activity.     

Design,Synthesis and Biological Activity of C3 Hemisynthetic Triterpenic Esters as Novel Antitrypanosomal Hits

Research for innovative drugs is crucial to contribute to parasitic infections control and eradication. Inspired by natural antiprotozoal triterpenes, a library of 12 hemisynthetic 3-O-arylalkyl esters was derived from ursolic and oleanolic acids through one-step synthesis. Compounds were tested on Trypanosoma, Leishmania and the WI38 cell line alongside with a set of triterpenic acids. Results showed that the triterpenic C3 esterification keeps the antitrypanosomal activity (IC₅₀≈1.6–5.5 μm ) while reducing the cytotoxicity compared to parent acids. Unsaturation of the ester alkyl chain leads to an activity loss interestingly kept when a sterically hindered group replaces the double bond or shields the ester group. An ursane/oleanane C3 hydroxylation was the only important feature for antileishmanial activity. Two candidates, dihydrocinnamoyl and 2-fluorophenylpropionyl ursolic acids, were tested on an acute mouse model of African trypanosomiasis with significant parasitemia reduction at day 5 post-infection for the dihydrocinnamoyl derivative. Further evaluation on other alkyl/protective groups should be investigated both in vitro and in vivo.     

Triterpene Acids from the Leaves of Planchonella Duclitan (Blanco) Bakhuizan

From the methanolic extract of the leaves of Planchonella duclitan, 2α,3α,19α,23‐tetrahydroxy‐13,27‐cyclours‐11‐en‐28‐oic acid (1), myrianthic acid (2), 2‐hydroxyursolic acid (3), ursolic acid (4), pomolic acid (5), rotundic acid (6), and jacoumaric acid (7) were isolated, and their structures were elucidated on the basis of their spectroscopic analysis. Among them, compound 1 was a new cyclopropyl ursane‐type triterpene acid. Additionally, compounds 4 and 7 showed significant cytotoxicity toward human colorectal carcinoma cell line HT29 and human breast carcinoma cell line MCF‐7 with IC₅₀ values ranging from 5.8 ± 1.4 to 6.5 ± 1.9 μM.     

Studies on differentiation-inducing activities of triterpenes.

Differentiation-inducing activity of over 180 extracts of crude drugs and plants was tested using mouse myeloid leukemia cell line (M1). The methanol extracts of clove (Syzygium aromaticum Merrill et Perry, Myrtaceae) showed remarkable induction of differentiation of M1 cells into macrophage-like cells. From the extract, oleanolic acid (1) and crategolic acid (2) were isolated as the active components. We also tested other triterpenes, such as oleananes, ursanes and dammaranes, to investigate the structure-activity relationship. Some triterpene aglycones showed differentiation-inducing activity, but triterpene glycosides showed little activity. Furthermore, the differentiation-inducing activity of these triterpene compounds was tested against human acute promyelocytic leukemia cell line (HL-60).     

Phenolic and Triterpenoid Glycosides from Pyrola calliantha

Pyrocallianthasides A ( 1 ) and B ( 2 ), a new dimer and a new mono‐deglucosyl trimer of homoarbutin (=4‐hydroxy‐3‐methylphenyl β‐glucopyranoside), and callianthaside A ( 3 ), a new ursane‐type triterpene glycoside, together with three known phenolic glycosides and three known ursane‐type triterpenoids, were isolated from the whole plants of Pyrola calliantha. The structures of 1 – 3 were elucidated by chemical and spectroscopic methods.     

Determination of Triterpene Acids from 37 Different Varieties of Raspberry using Pre-column Derivatization and HPLC Fluorescence Detection

In this work, we have developed an efficient method for the rapid extraction and separation of triterpene acids from 37 different varieties of raspberry via ultrasound-assisted dispersive liquid–liquid microextraction (UA-DLLME). The triterpene acids were then determined by high-performance liquid chromatography (HPLC) with fluorescence detection using benzimidazo-[2,1-b]quinazolin-12(6H)-one-5-ethyl-p-toluenesulfonate (BQETS) as the labeling agent. Five triterpene acids, including asiatic acid (AA), maslinic acid (MA), corosolic acid (CA), oleanolic acid (OA) and betulinic acid (BA), were extracted by UA-DLLME using chloroform and acetone as the extracting and dispersing solvents, respectively. After extraction and nitrogen flushing, the extracts were simultaneously characterized by HPLC based on pre-column derivatization using BQETS, a new labeling agent synthesized in our laboratory. Several key parameters affecting the extraction efficiency and derivatization yields were investigated and optimized by response surface methodology (RSM) combined with Box–Behnken design (BBD). The method was further validated for linearity (correlation coefficient R ² > 0.9979), precision (RSD = 0.23–2.45 %), and recovery (RSD = 90–106.5 %). The limits of detection (LODs) and the limits of quantification (LOQs) were determined to be within the range of 1.83–7.69 µg/L and 6.06–25.47 µg/L, respectively. This is the first report of the use of BQETS as a pre-column derivatization agent for the determination of triterpene acids in real samples. The proposed method has been applied to the determination of five triterpene acids in 37 different raspberry varieties with significantly increased sensitivity compared to other methods. The results obtained indicate that the contents of triterpene acids vary significantly across different raspberry varieties.

     

A new triterpene saponin from Panax japonicus C. A. Meyer var major (Burk.) C. Y. Wu et K. M. Feng

<正>One new triterpene saponin was isolated from Panaxjaponicus C.A.Meyer var major(Burk.) C.Y.Wu et K.M.Feng,and established as oleanolic acid 3-O-[β-D-glucopyranosyl-(1→2)-β-D-glucuronopyranosyl-6'-O-n-butyl ester]which showed moderate antitumor activities against the A2780 cells and OVCAR-3 cells.Its structure was established by means of spectral data, particularly NMR,including HSQC and HMBC techniques.     

Cytotoxicity of two triterpenoids from Nigella glandulifera

During an investigation of antitumor substances from Nigella glandulifera Freyn et Sint. (Ranunculaceae) the cytotoxicity of two oleanane triterpene saponins isolated from the seeds of this species, kalopanaxsaponins A and I, was evaluated against HepG2, drug resistant HepG2 (R-HepG2) (two hepatocyte cell lines) and primary cultured normal mouse hepatocytes. Evident cytotoxic activities were observed. Morphological observations and cell cycle analysis suggest that these compounds inhibit the proliferation of hepatoma by inducing apoptosis and consequently kalopanaxsaponins A and I may be potential therapeutic agents for the treatment of parental and drug resistant hepatoma.     

Biosynthesis of baccharis oxide, a triterpene with a 3,10-oxide bridge in the A-ring

A new oxidosqualene cyclase (OSC) cDNA was cloned from the roots of Stevia rebaudiana. Functional expression in yeast and spectral analyses of the products established that the obtained OSC yields baccharis oxide as the major product. This is the first identification of an OSC yielding baccharis oxide. This result clearly demonstrated that baccharis oxide, a baccharane triterpene with a unique 3,10-oxide bridge in the A-ring, is a direct product from oxidosqualene by an OSC.     

A new acylated triterpene from the roots of Chaenomeles japonica

A new acylated triterpene together with prunasin, (-)-epicatechin, daucosterol, and three triterpenes, ursolic, oleanolic, and pomolic acids was isolated from the root of Chaenomeles japonica (THUNB.) LINDL. (Rosaceae) and determined to be 3-O-(E)-3, 5-dihydroxycinnamoylursolic acid on the basis of NMR and FAB-MS experiments.     

A Novel Ursane Triterpene from Rubus swinhoei

As a part of investigation on the plant of Rubus, we studied the chemical constituents of the roots of R. swinhoei. A novel ursane triterpene, named swinhoeic acid, was isolated and converted into its methyl-ester with CH2N2. This paper deals with its structure elucidation.Figure 1 The structure of 1 and 1a Figure 2 The key HMBC correlationsCompound 1a, was obtained as white powder, [?] - 66 (c 0.1, CHCl3). Its molecular formula was assigned as C31H48O5 by HR-EIMS ([M]+ m/z 500.3487…     

Enrichment and separation of antitumor triterpene acids from the epidermis of Poria cocos by pH‐zone‐refining counter‐current chromatography and conventional high‐speed counter‐current chromatography

Triterpene acids were extracted from the epidermis of Poria cocos (Schw.) Wolf. These acids were found to inhibit the growth of lung cancer cells in vitro and in vivo. An efficient method for the preparative separation of antitumor triterpene acids was established that involves the combination of pH‐zone‐refining counter‐current chromatography and conventional high‐speed counter‐current chromatography. We used pH‐zone‐refining counter‐current chromatography to concentrate the triterpene acids using a two‐phase solvent system composed of petroleum ether/ethyl acetate/methanol/water (3:7:5:5, v/v/v/v), trifluoroacetic acid (10 mM) was added to the upper phase as a retainer, and ammonia (10 mM) was added to the lower phase as an eluter. As a result, 200 mg concentrate of triterpene acids was obtained from 1.0 g of crude extract. The concentrate was further separated by conventional high‐speed counter‐current chromatography using a solvent system composed of petroleum ether/ethyl acetate/methanol/water (0.8:1.2:1.2:0.9, v/v), yielding 50 mg of poricoic acid A and 5 mg of poricoic acid B from 120 mg concentrate, respectively. The inhibitory activity of the major compound on lung A549 cells was examined and poricoic acid A was found to significantly inhibit the growth of A 549 cells.     

Comparison Between Methyl and Trimethylsilyl Ester Derivatives in the Separation and GC Quantification of Triterpene Acids in Eugenia brasiliensis Leaf Extract

This study details a method to characterize the triterpene acid-rich extract obtained from the defatted leaves of Eugenia brasiliensis (Myrtaceae) via extraction with 2 % NaOH in ethanol at room temperature. The crude extract (yield 2.35 %) was submitted to analysis by gas chromatography coupled to mass spectrometry (GC–MS) confirming ursolic acid as its major compound. The optimal conditions for the separation of oleanolic, betulinic and ursolic acids were assayed by GC with flame ionization detection (GC–FID) using two different columns (DB-5 and DB-17HT) and by applying two distinct derivatizing protocols. The use of a DB-17HT column led to the best results, with a shorter runtime and a better resolution (Rs) between the oleanolic and betulinic signals for both the bis-trimethylsilyl (Rs 2.84) and methyl ester derivatives (Rs 2.47). A DB-5 column also gave satisfactory results for the TMS ester, with a runtime of 30 min and Rs 2.14. Ursolic acid in the crude extract was quantified by comparison to two individual standard curves determined using commercial ursolic as its TMS derivative on the DB-5 column and its methyl ester on the DB-17HT column. Good linearity was achieved in both cases (r ² = 0.9776 and 0.9953, respectively), and the amounts of ursolic acid in the extracts were calculated to be 144.7 and 147.9 mg·g^?1, respectively. These results showed no significant differences when compared using Tukey’s HSD test. Total triterpene acids amounted to 0.52 % in E. brasiliensis dry leaves.     

齐墩果酸与熊果酸结构修饰物的药理活性和构效关系研究进展

齐墩果酸(OA)和熊果酸(UA)均属于五环三萜类化合物,广泛存在于自然界中,具有多种显著的生物活性。本文综述了近年来齐墩果酸及熊果酸结构修饰物的药理活性和构效关系的研究进展。     

A New Triterpene and New Sesquiterpenes from the Roots of Ligularia sagitta

One new triterpene and seven new eremophilane‐type sesquiterpenes were isolated from the roots of Ligularia sagitta, among them 1a , an O‐acetylated oleanane type triterpene, 2a and 3a , two 11‐nor eremophilane‐type sesquiterpenes, 4a, 5 , and 6 , three standard eremophilane‐type sesquiterpenes, and 7 and 8 , two tri‐nor eremophilane‐type sesquiterpenes. Their structures were established by extensive spectral analyses (1D, 2D‐NMR, IR, and MS). Compound 1a showed moderate cytotoxicity against two tumor cell lines.