- Application of positive mode atmospheric chemical ionisation to distinguish epimeric oleanolic and ursolic acids
-
A new and more reliable method is reported for distinguishing the equatorial and axial epimers of oleanolic and ursolic acids and related triterpenoids based primarily on the relative abundance of the [M + H]+ and [M + H - H2O]+ signals in their positive mode atmospheric pressure chemical ionisation mass spectra. The rate of elimination of water, which is the principal primary fragmentation of protonated oleanolic and ursolic acids, depends systematically on the stereochemistry of the hydroxyl group in the 3 position. For the b-epimer, in which the 3-hydroxyl substituent is in an equatorial position, [M + H - H2O]+ is the base peak. In contrast, for the a-epimer, where the 3-hydroxyl group is axial, [M + H]+ is the base peak. This trend, which is general for a range of derivatives of oleanolic and ursolic acids, including the corresponding methyl esters, allows epimeric triterpenoids in these series to be securely differentiated. Confrmatory information is available from the collision-induced dissociation of the [M + H - H2O]+ primary fragment ions, which follow different pathways for the species derived from axial and equatorial epimers of oleanolic and ursolic acids. These two pieces of independent spectral information permit the stereochemistry of epimeric oleanolic and ursolic acids (and selected derivatives) to be assigned with confdence without relying either on chromatographic retention times or referring to the spectra or other properties of authentic samples of these triterpenoids.
- Townley, Chloe,Brettell, Rhea C.,Bowen, Richard D.,Gallagher, Richard T.,Martin, William H.C.
-
-
Read Online
- Synthesis of novel [3,2-b] furan-fused pentacyclic triterpenoids via gold - Catalyzed intramolecular heterocyclization of 2-alkynyl-3-oxotriterpene acids
-
A direct and atom-economical synthetic route to new [3,2-b] furan-fused pentacyclic triterpenoids has been developed, using gold-catalyzed 5-exo-dig heterocyclization of accessible 2-alkynyl derivatives of betulonic, ursonic, and oleanonic acids.
- Gubaidullin, Rinat R.,Khalitova, Rezeda R.,Galimshina, Zulfiya R.,Spivak, Anna Yu
-
-
Read Online
- Oleanolic acid analogs as NO, TNF-α and IL-1β inhibitors: Synthesis, biological evaluation and docking studies
-
A series of oleanolic acid analogs, characterized by structural modifications at position C-3 and C-28 of oleanane skeleton were synthesized and assessed for antiinflammatory potential towards lipopolysaccharide (LPS) induced nitric oxide (NO) production
- Bhandari, Pamita,Patel, Neeraj Kumar,Gangwal, Rahul P.,Sangamwar, Abhay T.,Bhutani, Kamlesh Kumar
-
-
Read Online
- Type and position of linkage govern the cytotoxicity of oleanolic acid rhodamine B hybrids
-
Oleanolic acid/rhodamine B hybrids exhibit different cytotoxicity depending on the way these two structural elements are linked. While a hybrid holding a piperazinyl spacer at C-28 proved to be cytotoxic in the nano-molar concentration range, hybrids with a direct linkage of the Rho B residue to C-3 of the triterpenoid skeleton are cytotoxic only in the low micro-molar concentration range without any selectivity. This once again underlines the importance of selecting the right spacer and the most appropriate position on the skeleton of the triterpene to achieve the most cytotoxic hybrids possible.
- Heise, Niels,Hoenke, Sophie,Simon, Vivienne,Deigner, Hans-Peter,Al-Harrasi, Ahmed,Csuk, René
-
-
Read Online
- The analgesic and anti-inflammatory effect of new oleanolic acid acyloxyimino derivative
-
The new derivative of well-known triterpene, oleanolic acid: methyl 3-octanoyloxyiminoolean-12-en-28-oate 5, was synthesized by the action of caprylic acid on methyl oleanolate 3-oxime in the presence of dicyclohexylcarbodiimide in dioxane. The molecular structure of the obtained product 5 was confirmed by spectral methods. The acute toxicity, locomotor activity, and the dose-dependent analgesic activity were studied. In addition, the effect of compound 5 on morphine-induced analgesic activity, the dose-dependent anti-inflammatory activity and the effect of the compound on diclofenac anti-inflammatory activity study were performed. The results proved a low toxicity (LD50 > 2 g/kg) of the tested product 5, which affected neither vertical nor horizontal locomotor activity in the given range of doses. The triterpene 5 also produced centrally mediated (morphine-like) analgesic action; however, only in the highest dose. The synergistic analgesic activity of 5 and morphine in the doses of 30.0 and 300.0 mg/kg was found. Compound 5 expressed the anti-inflammatory action which did not affect the anti-inflammatory activity of diclofenac after their combined administration.
- Bednarczyk-Cwynar, Barbara,Zaprutko, Lucjusz,Marciniak, Joanna,Lewandowski, Grzegorz,Szulc, Michal,Kaminska, Ewa,Wachowiak, Natalia,Mikolajczak, Przemyslaw Lukasz
-
-
Read Online
- Novel oleanolic vinyl boronates: Synthesis and antitumor activity
-
A series of novel oleanane-type pentacyclic triterpenoids bearing a boronate ester moiety at C3 have been synthesized by palladium-catalyzed cross-coupling of bis(pinacolato)diboron with vinyl triflates, in the presence of base, and these compounds were fully characterized by 1D and 2D NMR techniques. Evaluation of their antiproliferative effects on a panel of hematological-based and solid tumor cell lines identified three active oleanolic vinyl boronates that inhibited the growth of leukemia (Jurkat, K562), Burkitt's lymphoma (Jijoye), cervix (Hela), colon (SW480), and ovary (SKOV-3) cancer cells without concomitant inhibition of non-tumoral human fibroblasts. Their mechanisms of action were investigated on the leukemia Jurkat cell line. The results show that the incorporation of boron in the oleanolic acid core combined with the presence of amide bonds afforded compounds with desirable biological effects such as apoptosis induction and inhibition of proteasomal activity on tumor cells, which makes them potential templates for further development in the anticancer drug setting.
- Moreira, Vania M.,Salvador, Jorge A.R.,Sim?es, Sérgio,Destro, Federica,Gavioli, Riccardo
-
-
Read Online
- Oleanolic acid oxime derivatives and their conjugates with aspirin modulate the NF-κB-mediated transcription in HepG2 hepatoma cells
-
The aim of this study was to evaluate the effect of new oleanolic acid oxime (OAO) derivatives and their conjugates with aspirin (ASP) on the expression and activation of NF-κB in human hepatoma HepG2 cells. OAO derivatives showed a stronger cytotoxic effect against HepG2 cells compared with their conjugates with aspirin. Moreover, conjugation of OAO with ASP led to enhanced downregulation of NF-κB expression and activation. Among the hybrids with ASP, compounds: 19, 3-(2-acetoxy)benzoyloxyiminoolean-12-en-28-oic acid morpholide and 13, 3-(2-acetoxy)benzoyloxyiminoolean-12-en-28-oic acid methyl ester, differing, respectively, in morpholide and methyl ester groups at the C-17 position of oleanolic acid (OA) molecule were the most efficient. COX-2 transcript and protein levels were also diminished after treatment with these compounds. The results of this study indicate that the new derivatives of OAO and particularly their conjugates with ASP, downregulate the expression of COX-2 in HepG2 cells by modulating the NF-κB signaling pathway and suggest their potential application in the prevention of liver inflammation and cancer.
- Krajka-Ku?niak, Violetta,Bednarczyk-Cwynar, Barbara,Paluszczak, Jaros?aw,Szaefer, Hanna,Naro?na, Maria,Zaprutko, Lucjusz,Baer-Dubowska, Wanda
-
-
Read Online
- Design and synthesis of novel oleanolic acid based chromenes as anti-proliferative and anti-inflammatory agents
-
A practical and novel approach has been developed for the synthesis of oleanolic acid based chromene analogues. Different α,β-unsaturated carbonyl and chromene derivatives of oleanolic acid were synthesized and evaluated for their anticancer activity. Compounds 6e, 6k, 7e and 7g showed significant anticancer activity within the IC50 range of 12.23-39.04 μg mL-1. The promising derivatives 7e and 7g were further analyzed for their effects on the cell cycle and apoptosis in A-549 and MDA-MB-231 cells, and it was depicted that 7e and 7g triggered apoptosis in A-549 and MDA-MB-231 cells and arrested the cell population in the G2/M phase. The anticancer activity of the most active analogue 7g occurred through microtubule destabilization (IC50: ~3.6 μg mL-1), and it was found to be non-toxic against human erythrocytes. The compounds 7e and 7g significantly inhibited the proinflammatory cytokines TNF-α and IL-6.
- Raghuvanshi, Dushyant Singh,Verma, Narsingh,Singh, Shilpi,Luqman, Suaib,Chand Gupta, Amit,Bawankule, Dnyaneshwar U.,Tandon, Sudeep,Nagar, Abhishek,Kumar, Yogesh,Khan, Feroz
-
-
Read Online
- Synthesis of novel heterocyclic oleanolic acid derivatives with improved antiproliferative activity in solid tumor cells
-
A series of new oleanane imidazole carbamates, N-acylimidazoles or N-alkylimidazoles were synthesized, characterized and evaluated for their antiproliferative activity in AsPC-1 pancreatic cancer cells. Structure-activity relationship analysis revealed that the N-alkylimidazole 27 was the most active compound with apoptosis induction abilities correlated with upregulation of NOXA and downregulation of Bcl-xL. The antiproliferative activity of compound 27 was further tested in more solid tumor cell lines with IC50 values lower than 1 μM.
- Leal, Ana S.,Wang, Rui,Salvador, Jorge A. R.,Jing, Yongkui
-
-
Read Online
- Beckmann rearrangement of oxime obtained from oleanolic acid. Structure elucidation of the initial oxime
-
Seven-membered A-lactam and A-nitrile of methyl oleanolate were synthesized from the corresponding oxime. Many reaction setups were tried to find the optimum conditions. The best results (the highest yield of the desired lactam along with total consumption of starting oxime) were obtained in pyridine with phosphoryl chloride as Lewis acid. The main product was obtained with the yield of about 60%. Mechanism of Beckmann rearrangement for the above triterpenic 3-oxime leading to normal and abnormal product (a lactam and a nitrile, respectively) was explained. The structures of both products were determined and fully characterized by spectral data. The stereoisomerism of the initial oxime was determined on the basis of Beckmann rearrangement product structure and X-ray analysis.
- Bednarczyk-Cwynar, Barbara,Zaprutko, Lucjusz,Froelich, Anna
-
-
Read Online
- Hybrid compounds strategy in the synthesis of oleanolic acid skeleton-NSAID derivatives
-
The current study focuses on the synthesis of several hybrid individuals combining a natural oleanolic acid skeleton and synthetic nonsteroidal anti-inflammatory drug moieties (NSAIDs). It studied structural modifications of the oleanolic acid structure by use of the direct reactivity of hydroxyl or hydroxyimino groups at position C-3 of the triterpenoid skeleton with the carboxylic function of anti-inflammatory drugs leading to new perspective compounds with high potential pharmacological activities. Novel ester- and iminoester-type derivatives of oleanolic unit with the different NSAIDs, such as ibuprofen, aspirin, naproxen, and ketoprofen, were obtained and characterized. Moreover, preliminary research of compounds obtaining structure stability under acidic conditions was examined and the PASS method of prediction of activity spectra for substances was used to estimate the potential biological activity of these compounds.
- Pawe?czyk, Anna,Olender, Dorota,Sowa-Kasprzak, Katarzyna,Zaprutko, Lucjusz
-
-
Read Online
- Electrophilic Triterpenoid Enones: A Comparative Thiol-Trapping and Bioactivity Study
-
Bardoxolone methyl (1) is the quintessential member of triterpenoid cyanoacrylates, an emerging class of bioactive compounds capable of transient covalent binding to thiols. The mechanistic basis for this unusual "pulsed reactivity" profile and the mode of its biological translation are unknown. To provide clues on these issues, a series of Δ1-dehydrooleanolates bearing an electron-withdrawing group at C-2 (7a-m) were prepared from oleanolic acid (3a) and comparatively investigated in terms of reactivity with thiols and bioactivity against a series of electrophile-sensitive transcription factors (Nrf2, NF-κB, STAT3). The emerging picture suggests that the triterpenoid scaffold sharply decreases the reactivity of the enone system by steric encumbrance and that only strongly electrophilic and sterically undemanding substituents such as a cyanide or a carboxylate group can re-establish Michael reactivity, albeit in a transient way for the cyanide group. In general, a substantial dissection between the thiol-trapping ability and the modulation of biological end-points sensitive to thiol alkylation was observed, highlighting the role of shape complementarity for the activity of triterpenoid thia-Michael acceptors.
- Del Prete, Danilo,Taglialatela-Scafati, Orazio,Minassi, Alberto,Sirignano, Carmina,Cruz, Cristina,Bellido, Maria L.,Mu?oz, Eduardo,Appendino, Giovanni
-
-
Read Online
- Chemical modification of oleanene type triterpenes and their inhibitory activity against HIV-1 protease dimerization
-
Oleanolic acid derivatives with different lengths of 3-O-acidic acyl chains were synthesized and evaluated for their inhibitory activity against HIV-1 protease. The lengths of the acidic chains were optimized to 6 and 8 carbons. Changing a 3-ester bond to an amide bond or dimerization of the triterpenes retained their inhibitory activity against HIV-1 protease. Introduction of an additional acidic chain to C-28 of oleanolic acid increased the inhibitory activity appreciably, though a derivative with only one acidic chain linked at C-28 also showed potent activity against HIV-1 protease. The inhibitory mechanism was proved directly by size exclusion chromatography to be inhibition of dimerization of the enzyme polypeptides. The ester bonds of the triterpene derivatives were found to be stable to lipase under mild alkaline conditions.
- Ma,Nakamura,Hattori
-
-
Read Online
- Incorporation of a Michael acceptor enhances the antitumor activity of triterpenoic acids
-
Finding and developing drugs for the treatment of cancer has been challenging scientists for many decades, and using compounds of natural origin represents one of several strategies. Triterpenoic acids are a very promising class of secondary metabolites being able to induce apoptosis while their cytotoxicity is low. Therefore, derivatizations have to be conducted to improve cytotoxicity while retaining their ability to induce programmed cell death. The incorporation of a Michael acceptor into molecules resulted very often in drugs of improved cytotoxicity. Thus, in this study we synthesized and evaluated several Michael acceptor substituted compounds derived from glycyrrhetinic, ursolic, oleanolic and platanic acid. The influence of the presence of such a functional group onto the cytotoxicity was investigated in colorimetric sulforhodamine B assays employing several human cancer cell lines. EC50 values in the single-digit micromolar range were measured. Thus, the incorporation of a Michael acceptor unit into triterpenoic acids enhances the cytotoxicity of these compounds significantly.
- Heller, Lucie,Schwarz, Stefan,Perl, Vincent,K?witsch, Alexander,Siewert, Bianka,Csuk, René
-
-
Read Online
- Cytotoxicity of oleanolic and ursolic acid derivatives toward hepatocellular carcinoma and evaluation of NF-κB involvement
-
Oleanolic and ursolic acids are two ubiquitous isomeric triterpene phytochemicals known for their anticancer activity. A set of derivatives of the two compounds with a modified oxidation state and lipophylicity at C-3 and C-28 positions, were prepared and tested as anticancer agents versus the lines HepG2, Hep3B and HA22T/VGH of hepatocarcinoma, a strongly aggressive tumor that is not responsive toward the standard therapies. New derivatives containing a three carbons side chain on the C-3 position were synthetized in both stereoisomeric forms by the Barbier-Grignard procedure and three of them were found to be active toward all of the three targets. The implication of the transcriptional nuclear factor NF?κB in the mechanism of action was assessed for the more active compounds in the set, as hepatocellular carcinoma (HCC) cyto-types are known to overexpress NF?κB.
- Fontana, Gianfranco,Bruno, Maurizio,Notarbartolo, Monica,Labbozzetta, Manuela,Poma, Paola,Spinella, Alberto,Rosselli, Sergio
-
-
- COMPOSITIONS COMPRISING ACIDIC EXTRACTS OF MASTIC GUM AND USES THEREOF FOR TREATING OPTIC NEUROPATHY
-
The invention relates to compositions and formulations comprising isolated acidic fraction of mastic gum and uses thereof for treating optic neuropathy conditions.
- -
-
-
- COMPOSITIONS COMPRISING TRITERPENOIDS AND USES THEREOF FOR TREATING OPTIC NEUROPATHY
-
The invention relates to compositions and formulations comprising at least one triterpenoic acid and at least one neutral triterpenoid and uses thereof for treating optic neuropathy conditions.
- -
-
-
- Synthesis and cytotoxic activity of triterpenoid thiazoles derived from allobetulin, methyl betulonate, methyl oleanonate, and oleanonic acid
-
A total of 41 new triterpenoids were prepared from allobetulone, methyl betulonate, methyl oleanonate, and oleanonic acid to study their influence on cancer cells. Each 3-oxotriterpene was brominated at C2 and substituted with thiocyanate; subsequent cyclization with the appropriate ammonium salts gave N-substituted thiazoles. All compounds were tested for their in vitro cytotoxic activity on eight cancer cell lines and two non-cancer fibroblasts. 2-Bromoallobetulone (2b) methyl 2-bromobetulonate (3b), 2-bromooleanonic acid (5b), and 2- thiocyanooleanonic acid (5c) were best, with IC50 values less than 10 mm against CCRF-CEM cells (e.g., 3b: IC50=2.9 μm) as well as 2'-(diethylamino)olean-12(13)-eno[2,3-d]thiazole-28-oic acid (5 f, IC50=9.7 μm) and 2'-(N-methylpiperazino)olean-12(13)-eno[2,3-d]thiazole-28-oic acid (5k, IC50=11.4 μm). Compound 5c leads to the accumulation of cells in the G2 phase of the cell cycle and inhibits RNA and DNA synthesis significantly at 1xIC50. The G2/M cell-cycle arrest probably corresponds to the inhibition of DNA/RNA synthesis, similar to the mechanism of action of actinomycin D. Compound 5c is new, active, and nontoxic; it is therefore the most promising compound in this series for future drug development. Methyl 2-bromobetulonate (3b) and methyl 2-thiocyanometulonate (3c) were found to inhibit nucleic acid synthesis only at 5xIC50. We assume that in 3b and 3c (unlike in 5c), DNA/RNA inhibition is a nonspecific event, and an unknown primary cytotoxic target is activated at 1xIC50 or lower concentration.
- Borkova, Lucie,Adamek, Richard,Kalina, Petr,Dra?ar, Pavel,Dzubak, Petr,Gurska, Sona,Rehulka, Jiri,Hajduch, Marian,Urban, Milan,Sarek, Jan
-
p. 390 - 398
(2017/12/07)
-
- COMPOSITIONS COMPRISING TRITERPENOIDS
-
The invention relates to compositions and formulations comprising at least one triterpenoic acid and at least one neutral triterpenoid and uses thereof for treating for use in treating a condition selected from Alzheimer's disease (AD), Parkinson's Diseases (PD) and vascular dementia (VD).
- -
-
-
- Effective synthesis of novel furan-fused pentacyclic triterpenoids via anionic 5-exo dig cyclization of 2-alkynyl-3-oxotriterpene acids
-
An efficient synthetic route to biologically interesting furan-fused pentacyclic triterpenoids with a furan moiety 2,3-annelated to the terpenoid skeleton has been developed. New heterocyclic triterpenoids have been obtained in moderate to good yields by base-promoted 5-exo-dig cyclization of the pent-4-yn-1-one moiety in ring А of the 2-alkynyl-3-oxotriterpene acids of lupane, ursane and oleane type.
- Gubaidullin, Rinat R.,Yarmukhametova, Darina S.,Nedopekina, Darya A.,Khalitova, Rezeda R.,Spivak, Anna Yu.
-
p. 100 - 116
(2017/08/10)
-
- Hybrids of oleanolic acid with norbornene-2,3-dicarboximide-n-carboxylic acids as potential anticancer agents
-
The synthesis and cytotoxic activity of new oleanolic acid derivatives (8anc and 9anc) are presented. The obtained compounds are hybrids of oleanolic acid oximes and carboxylic acids containing short alkyl chains linked with nitrogen atom of norbornene-2,3-dicarboximide moieties via the nitrogen atom. The structures of the obtained new compounds (8anc and 9anc) were confirmed by spectral data. The derivatives 8anc and 9anc were subjected to the MTT assay in order to evaluate their cytotoxic activity towards HeLa, KB, MCF-7, HepG2 and HDF cell lines in comparison to mother compound (oleanolic acid, 1). Among the tested oximes acylated with carboxylic acids containing norbornene-imide moieties, the derivative 8b, with a propionoxyimino linker, exhibited the most advantageous level of cytotoxicity, with IC50 values from 2.75 μM (for MCF-7 cells) to 4.36 μM (for HDF cells).
- Bednarczyk-Cwynar, Barbara,Ruszkowski, Piotr,Atamanyuk, Dmytro,Lesyk, Roman,Zaprutko, Lucjusz
-
p. 827 - 835
(2017/06/05)
-
- Synthesis and biological evaluation of oleanolic acid derivative-chalcone conjugates as α-glucosidase inhibitors
-
α-Glucosidase is a promising target for the treatment of obesity and diabetes mellitus. A series of oleanolic acid derivative-chalcone conjugates were designed and synthesized as α-glucosidase inhibitors. Their structures were determined by spectroscopic analysis and their α-glucosidase inhibitory activities were investigated in vitro. Most conjugates exhibited moderate inhibitory activity against α-glucosidase; among them, conjugate 1b (IC50 = 3.2 ± 0.2 μM) possessed the strongest α-glucosidase inhibitory activity, and the preliminary structure-activity relationship showed that the furan or thiophene rings in the chalcone units of the conjugates had a tendency to enhance the activity. Lineweaver-Burk plot analysis demonstrated competitive inhibition of α-glucosidase activity by 1b, 6b, 5c and 4d; their inhibition constant (Ki) values were 16.6, 29.3, 14.6 and 20.6 μM, respectively. The interaction forces between the conjugates and α-glucosidase were hydrogen bonding and van der Waals.
- Tang, Chu,Zhu, Linhui,Chen, Yu,Qin, Rui,Mei, Zhinan,Xu, Jing,Yang, Guangzhong
-
p. 10862 - 10874
(2014/03/21)
-
- 2-SUBSTITUTED OLEANOLIC ACID DERIVATIVE, METHOD PREPARING FOR SAME, AND APPLICATION THEREOF
-
The present invention belongs to the field of natural medicine and pharmaceutical chemistry, and specifically relates to novel 2-substituted oleanolic acid derivatives of formula (I) or a pharmaceutically acceptable salt thereof, to a process for the preparation of these compounds, compositions containing such compounds and their use in preparing antineoplastic medicaments.
- -
-
Paragraph 0073
(2014/10/16)
-
- 2-SUBSTITUTED OLEANOLIC ACID DERIVATIVE, METHOD PREPARING FOR SAME, AND APPLICATION THEREOF
-
The present invention belongs to the field of natural medicine and pharmaceutical chemistry, and specifically relates to novel 2-substituted oleanolic acid derivatives of formula (I) or a pharmaceutically acceptable salt thereof, to a process for the preparation of these compounds, compositions containing such compounds and their use in preparing antineoplastic medicaments.
- -
-
Paragraph 0074
(2014/12/09)
-
- Intermolecular Conjugate Addition of Pyrroloindoline and Furoindoline Radicals to α,β-Unsaturated Enones via Photoredox Catalysis
-
We have developed an intermolecular conjugate addition of 3a-pyrroloindoline/furoindoline radicals to α,β-unsaturated enones, through visible-light photoredox catalysis. Ir(ppy)2(dtbbpy) PF6 was found to be an effective promoter to initiate this reaction from readily available 3a-bromopyrroloindolines/furoindolines. This method was exploited to prepare a series of indole terpenoid-like compounds of potential biological interest.
- Zhou, Shupeng,Zhang, Deliang,Sun, Yu,Li, Ruofan,Zhang, Wenhao,Li, Ang
-
supporting information
p. 2867 - 2872
(2016/02/18)
-
- Synthesis of novel ring-A fused hybrids of oleanolic acid with capabilities to arrest cell cycle and induce apoptosis in breast cancer cells
-
Six novel oleanolic acid ring-A fused hybrids (5-10) have been synthesized by employing a four step protocol with the introduction of benzylidene functionality at C-2 as the key step. Their structures were established by high resolution NMR and Mass spectral data. The synthesized compounds have been screened against seven human cancer cell lines including ME-180 & HeLa (cervix), MCF-7, MDA-MB-453 & MDA-MB-231 (breast), PC-3 (prostate) and HT-29 (colon) using MTT assay. Most significantly, compound 10 showed potent activity against the three breast cancer cell lines. The IC50 value (10.60 μM) of compound 10 against MCF-7 found to be much lower than that of the standards and parent compound. Flow cytometric analysis reveals that compound 10 arrests cell cycle in S phase and induces apoptosis in MCF cells.2014 Elsevier Masson SAS. All rights reserved.
- Mallavadhani, Uppuluri Venkata,Vanga, Nagi Reddy,Jeengar, Manish Kumar,Naidu
-
p. 398 - 404
(2014/03/21)
-
- Anticancer effect of A-ring or/and C-ring modified oleanolic acid derivatives on KB, MCF-7 and HeLa cell lines
-
New A-ring or/and C-ring modified methyl oleanolate derivatives were prepared. New simple method of synthesis of 3,12-diketone (3) from methyl oleanonate (2) was worked out. The obtained new compounds were tested for cytotoxic activity on KB, MCF-7 and HeLa cell lines. The derivatives had acetoxy, oxo or hydroxyimino function at the C-3 position and in some cases oxo, hydroxyimino or acyloxyimino group at the C-12 position. Almost all of the compounds showed strong cytotoxic activity, higher than unchanged oleanolic acid. The most active substances turned out to be the derivatives with acyloxyimino function, especially 4 and 8d. The Royal Society of Chemistry 2012.
- Bednarczyk-Cwynar, Barbara,Zaprutko, Lucjusz,Ruszkowski, Piotr,Hladon, Boguslaw
-
scheme or table
p. 2201 - 2205
(2012/04/10)
-
- Synthesis and biological evaluation of oleanolic acid derivatives as inhibitors of protein tyrosine phosphatase 1B
-
Protein tyrosine phosphatase 1B (PTP1B) is a negative regulator in the process of insulin signaling and a promising drug target for diabetes and obesity. Derivatives of oleanolic acid were synthesized and evaluated as PTP1B inhibitors. Several derivatives exhibited moderate to good inhibitory activities against PTP1B, with 25f displaying the most promising inhibition (IC 50 = 3.12 μM). Structure-activity relationship analyses of these derivatives demonstrated that the integrity of the A ring and 12-ene moieties was important in the retention of PTP1B enzyme inhibitory activities. In addition, hydrophilic and acidic groups as well as the distance between the oleanene and acid moieties were associated with PTP1B inhibitory activities. Possible binding modes of 25f were explored by molecular docking simulations.
- Qian, Shan,Li, Haijiao,Chen, Yin,Zhang, Weiyu,Yang, Shengyong,Wu, Yong
-
scheme or table
p. 1743 - 1750
(2011/03/18)
-
- Different pathways for the deoxygenation of the A-ring of natural triterpene compounds
-
Some deoxygenation pathways were tested to remove the hydroxyl groups of the natural triterpenes oleanolic acid and maslinic acid to obtain a practical starting material for the semisynthesis of other interesting organic synthons. Different deoxygenation processes were carried out starting from these triterpenic acids or from several derivatives such as methyl esters and epoxy derivatives. The hydroxyl groups were transformed into some intermediate compounds including xanthyl, thiocarbonyl or tosyl derivatives. The opening of the oxirane ring between C-2 and C-3 was also achieved through different methods using deoxygenating reagents such as Me3SiCl/NaI, WCl 4/n-BuLi and Cp2TiCl.
- Parra, Andres,Lopez, Pilar E.,Garcia-Granados, Andres
-
experimental part
p. 177 - 196
(2010/05/18)
-
- Oleanolic acid and its derivatives: New inhibitor of protein tyrosine phosphatase 1B with cellular activities
-
Protein tyrosine phosphatase 1B is a key factor in the negative regulation of insulin pathway and a promising target for treatment of diabetes and obesity. Herein, a series of competitive inhibitors were optimized from oleanolic acid, a natural triterpenoid identified against PTP1B by screening libraries of traditional Chinese medicinal herbs. Modifying at 3 and 28 positions, we obtained compound 13 with a Ki of 130 nM, which exhibited good selectivity between other phosphatases involved in insulin pathway except T-cell protein tyrosine phosphatase. Further evaluation in cell models illustrated that the derivatives enhanced insulin receptor phosphorylation in CHO/hIR cells and also stimulated glucose uptake in L6 myotubes with or addition of without insulin.
- Zhang, Yi-Nan,Zhang, Wei,Hong, Di,Shi, Lei,Shen, Qiang,Li, Jing-Ya,Li, Jia,Hu, Li-Hong
-
p. 8697 - 8705
(2008/12/23)
-
- Remote hydroxylation of methyl groups by regioselective cyclopalladation. Partial synthesis of hyptatic acid-A
-
(Chemical Equation Presented) Hyptatic acid-A (32), a 2α,3β,24- trihydroxyolean-12-en-28-oic acid, previously isolated from Hyptis capitata, was obtained from maslinic acid (2). The regioselective cyclopalladation of the axial methyl group on C-4 of maslinic acid afforded the C-24 hydroxymethylene group due to the presence of a C-2-OR substituent. Nevertheless, hederagenin (7) (23-hydroxy derivative) was formed when this oxygenated group was not present.
- Garcia-Granados, Andres,Lopez, Pilar E.,Melguizo, Enrique,Parra, Andres,Simeo, Yolanda
-
p. 3500 - 3509
(2008/02/03)
-
- Triterpenoids. Part 21: Oleanolic acid azaderivatives as percutaneous transport promoters
-
Some new oleanolic acid derivatives with lactame and thiolactame structures in the A- or C-ring were prepared and tested as percutaneous transport promoters in vitro. Their activity was comparable with activity of N-dodecylcaprolactame (Azone). A-Thiolactame derivative of methyl oleanolate (13) was the most effective compound.
- Zaprutko, Lucjusz,Partyka, Danuta,Bednarczyk-Cwynar, Barbara
-
p. 4723 - 4726
(2007/10/03)
-
- Gastroprotective activity of oleanolic acid derivatives on experimentally induced gastric lesions in rats and mice
-
The gastroprotective effect of the triterpene oleanolic acid (OA) was assessed on gastric ulceration in rats. The effect of a single oral dose of OA was evaluated at 50, 100 and 200 mg kg-1 in the following models: pylorus ligature (Shay), and aspirin-and ethanol-induced gastric ulcers. A single oral administration of OA at doses of 50, 100 and 200 mg kg-1 inhibited the appearance of gastric lesions induced by ethanol, aspirin and pylorus ligature. In the pylorus ligature and aspirin models, the effect of OA at the selected concentrations was comparable with that of ranitidine at 50 mg kg-1. In the ethanol-induced gastric lesion model, OA showed a dose-dependent activity, and at 100 and 200 mg kg-1 was as active as omeprazole at 20 mg kg-1. The effect of OA, its acetylated and methoxylated derivatives, oleanonic acid and its methyl ester were assessed on HCl/ethanol-induced ulcers in mice at 200 mg kg-1. OA and its methoxylated (OAM) and acetylated (OAAM, OAA) derivatives proved to be active in this animal model. The semisynthetic derivatives OAM and OAAM had the greatest gastroprotective activity, but their effect was not significantly greater than OA. In an acute toxicity test on mice, intraperitoneal administration of OA showed no toxicity at doses up to 600 mg kg-1.
- Astudillo, Luis,Rodriguez, Jaime A.,Schmeda-Hirschmann, Guillermo
-
p. 583 - 588
(2007/10/03)
-
- Semi-synthesis of triterpene A-ring derivatives from oleanolic and maslinic acids. Part II. Theoretical and experimental 13C chemical shifts
-
Maslinic acid was obtained from olive-pressing residues, an several derivatives were formed. Rearrangements of 2-tosyloxy-derivatives of methyl maslinate made out by acetolysis. The main product of these rearrangements contained a cyclopentanic A-ring as
- Garcia-Granados, Andres,Duenas, Jose,Melguizo, Enrique,Moliz, Juan N.,Parra, Andres,Perez, Felipe L.
-
p. 653 - 670
(2007/10/03)
-
- Semi-synthesis of Triterpene A-Ring Derivatives from Oleanolic and Maslinic Acids. Theoretical and Experimental 13C Chemical Shifts
-
Oleanolic and maslinic acids were isolated from solid waste from olive oil and several derivatives were semi-synthesised using typical reaction procedures. Rearrangements of methyl oleanate by mesylation or treatment with phosphorus pentachloride were accomplished. Six rearranged products were obtained from these reactions, three of which were 3(4) -> 5-abeo compounds formed by A-ring contraction of the oleanene skeleton. Experimental 13C NMR chemical shifts for 21 compounds are given and a discussion of the substituent effects on their 13C shieldings are also included. Morover, theoretical 13C NMR chemical shifts, with the GIAO method calculated at the MM+ geometries using the B3LYP/6-31G* level, showed good agreement with the experimental, allowing a correct assignment for the experimental shifts.
- Garcia-Granados, Andres,Duenas, Jose,Moliz, Juan N.,Parra, Andres,Perez, Felipe L.,Dobado, J. A.,Molina, Jose
-
p. 326 - 339
(2007/10/03)
-
- New enone derivatives of oleanolic acid and ursolic acid as inhibitors of nitric oxide production in mouse macrophages
-
New derivatives of 3-oxoolean-1-en-28-oic acid and 3-oxours-1-en-28-oic acid were synthesized. Nine of them showed significant inhibitory activity against interferon-γ-induced nitric oxide production in mouse macrophages when assayed at the 1 μM level. 3,12-Dioxoolean-1,9-dien-28-oic acid (3) had the highest activity (IC50, 0.9 μM).
- Honda, Tadashi,Finlay, Heather J.,Gribble, Gordon W.,Suh, Nanjoo,Sporn, Michael B.
-
p. 1623 - 1628
(2007/10/03)
-
- Studies on the Constituents of Boschniakia rossica FEDTSCH. et FLEROV. I. Isolation and Structures of New Phenylpropanoid Glycosides, Rossicasides B, C and D
-
Besides p-coumaric acid, methyl p-coumarate, β-sitosterol, oleanolic acid and 3-epi-oleanolic acid, three new phenylpropanoid glycosides, rossicasides B, C and D were isolated from fresh plants of Boschniakia rossica (CHAM. et SCHLTDL.) FEDTSCH. et FLEROV (Orobanchaceae).The structures of rossicasides B, C and D were established as p-hydroxycinnamyl alcohol 1-O-β-D-glucopyranosyl(1->4)-α-L-rhamnopyranosyl(1->3)-β-D-(4-O-caffeyl)-glucopyranoside (1), p-hydroxycinnamyl alcohol 1-O-β-D-glucopyranosyl(1->2)-β-D-(6-O-p-coumaryl)-glucopyranoside (2), and p-hydroxycinnamyl alcohol 1-O-β-D-glucopyranosyl(1->2)-β-D-(4-O-p-coumaryl)-glucopyranoside (3), respectively.Keywords - phenylpropanoid glycoside; rossicaside B; rossicaside C; rossicaside D; Orobanchaceae; Boschniakia rossica; parasitic plant; 3-epi-oleanolic acid; oleanolic acid
- Konishi, Tenji,Shoji, Junzo
-
p. 2807 - 2815
(2007/10/02)
-