- Complete assignment of 1H and 13C NMR spectra of new pentacyclic triterpene acid benzyl esters
-
Complete assignments of 1H and 13C NMR chemical shifts for newly synthesized benzyl esters of oleanolic, ursolic and crataegolic acid based on DEPT, HSQC, HMBC, COSY, TOCSY, NOE and ROESY experiments are reported. Copyright
- Weis, Robert,Seebacher, Werner
-
-
Read Online
- Oleanolic acid-amino acids derivatives: Design, synthesis, and hepatoprotective evaluation in vitro and in vivo
-
Activated hepatic stellate cells (HSCs) are the main extracellular matrix (ECM)-producing cells in the injured liver and the key mediators of liver fibrosis; they also promote the progression of hepatocellular carcinoma (HCC). In the acidic extracellular
- Chu, Fuhao,Zhang, Wenxi,Guo, Wenbo,Wang, Zhaoyi,Yang, Yuqin,Zhang, Xinyu,Fang, Kang,Yan, Mengmeng,Wang, Penglong,Lei, Haimin
-
-
Read Online
- Semi-synthesis and antiproliferative evaluation of PEGylated pentacyclic triterpenes
-
Several PEGylated derivatives of oleanolic and maslinic acids have been semi-synthesized, attaching one acid-PEG reagent to the hydroxyl group/s at C-2 or C-2/C-3 of the A rings of these natural triterpenes, and also to their corresponding C-28 benzyl derivatives. Several monomeric and dimeric PEGylated compounds have also been produced by linking one diamine-PEG reagent to the carboxyl group at C-28 of the same natural triterpenes and also to their corresponding C-2 or C-2/C-3 acetylated derivatives. The cytotoxic effects of 12 triterpenic PEGylated derivatives in three cancer-cell lines (B16F10, HT29, and Hep G2) have been assayed. The best results have been achieved by the PEGylated-amine derivative of oleanolic acid, with IC50 concentrations between 0.22 and 3.78 μM, being between 28- and 963-fold more effective than its natural precursor. The percentages of apoptosis induction have also been determined for the five PEGylated derivatives with the lowest cytotoxicity data. All five compounds showed apoptotic effects on the treated cells, with a total apoptosis rate of 99% in the B16F10 cells, 80% in the Hep G2 cells, and 51% in the HT29 cells. We have also studied the changes in the mitochondrial membrane potential (MMP) to elucidate the possible mechanism involved in the apoptotic responses (intrinsic or extrinsic). Finally, to verify the results found in the cytometry assays, we have used fluorescence microscopy techniques to determine changes in the cell morphology. These PEGylated derivatives of natural triterpenoids, which can induce apoptosis at very low concentrations in different tumour lines, may represent new effective therapeutic drugs against these diseases.
- Medina-O'Donnell, Marta,Rivas, Francisco,Reyes-Zurita, Fernando J.,Martinez, Antonio,Martin-Fonseca, Samuel,Garcia-Granados, Andres,Ferrer-Martín, Rosa M.,Lupia?ez, Jose A.,Parra, Andres
-
-
Read Online
- Rapid Self-Healing and Thixotropic Organogelation of Amphiphilic Oleanolic Acid-Spermine Conjugates
-
Natural and abundant plant triterpenoids are attractive starting materials for the synthesis of conformationally rigid and chiral building blocks for functional soft materials. Here, we report the rational design of three oleanolic acid-triazole-spermine
- ?zdemir, Zulal,?aman, David,Bertula, Kia,Lahtinen, Manu,Bednárová, Lucie,Pazderková, Markéta,Rárová, Lucie,Nonappa,Wimmer, Zdeněk
-
p. 2693 - 2706
(2021/03/15)
-
- Synthesis and antitumor activity evaluation of oleanolic acid saponins bearing an acetylated L-arabinose moiety
-
A series of oleanolic acid derivatives bearing acetyl-substituted L-arabinose moiety has been synthesized and screened in vitro for cytotoxicity against ten cancer cell lines and four normal cell lines. The antiproliferative evaluation indicated that synt
- Zhong, Ye,Li, Hui-ning,Zhou, Lin,Su, Hua-sheng,Cheng, Mao-sheng,Liu, Yang
-
-
- Pentacyclic triterpenoid TGR5 receptor stimulant, preparation method and application thereof
-
The invention discloses a pentacyclic triterpenoid TGR5 receptor stimulant, a preparation method and application of the pentacyclic triterpenoid TGR5 receptor stimulant. The structure of the pentacyclic triterpenoid TGR5 receptor stimulant is as shown in a formula I, and the definition of each substituent is as shown in the specification and claims. According to the pentacyclic triterpenoid compound, the solubility is increased, the permeability is improved, the TGR5 receptor agonist activity is remarkably improved, Caco-2 monolayer cells can be penetrated, and the in-vivo drug effect exertion of the compound after oral administration is guaranteed. The TGR5 receptor stimulant is expected to be further developed into a medicine for treating metabolic diseases represented by diabetes.
- -
-
Paragraph 0123; 0329-0331
(2021/04/26)
-
- Oleanolic acid and δ - oleanolic acid derivative and medical application thereof (by machine translation)
-
The invention discloses a derivative of a pentacyclic triterpene novel AMPK agonist oleanolic acid and δ - oleanolic acid and a medical application thereof, in particular to a compound shown in formula I or formula II. A pharmaceutically acceptable salt or ester or solvate thereof, which can be used to prepare AMPK agonists with enhanced AMPK phosphorylation level activity and to the preparation of drugs for preventing or treating AMPK mediated diseases. The novel pentacyclic triterpene compound has remarkable AMPK agonist activity, and the activity is remarkably superior to the recognized AMPK agonist AICICAR, and meanwhile, the novel pentacyclic triterpene compound has pharmacokinetic properties such as better oral bioavailability and very good safety. (by machine translation)
- -
-
Paragraph 0125-0128; 0547-0550
(2021/01/15)
-
- Oleanolic acid C-3-site sugar conjugate, preparation method and anti-influenza virus application thereof
-
The invention provides an oleanolic acid-C-3-site sugar conjugate with a structure shown as a formula (I) or pharmaceutically acceptable salt thereof and a preparation method thereof. The oleanolic acid-C3-site sugar conjugate has an obvious inhibiting effect on influenza viruses and can be used for preparing a medicine for preventing or treating influenza and a drug for preventing or inhibiting the entry of influenza viruses into cells.
- -
-
Paragraph 0035-0036; 0041
(2020/12/05)
-
- Nematicidal activity of oleanolic acid derivatives on Meloidogyne incognita
-
In this study, oleanolic acid and its derivatives were studied for their invivo nematicidal activity against root-knot nematode (RKN) Meloidogyne incognita. A series of C-28-oleanolates including five new (5, 7–10) and seven known (1–4, 6, 11, 12) compounds were synthesised and their nematicidal activity was determined and compared with the standard nematicide furadan for the first time. The structures of the compounds were elucidated through 1H NMR, 13C NMR and EIMS. Compounds 4, 5, 7, 8 and 10 showed ~ 90percent inhibition of RKN at 0.125percent concentration after 72 h showing their potential use in nematicidal control.
- Ayub, Anjum,Bano, Zarina,Begum, Sabira,Fayyaz, Shahina,Hassan, Nabila,Iqbal, Erum,Kiran, Zareena,Sara, Sara,Siddiqui, Bina S.
-
-
- Oleanolic acid derivative with conjugated diene structure C ring and preparation method and application thereof
-
The invention belongs to the field of medicinal chemistry, and particularly relates to an oleanolic acid derivative with a conjugated diene structure C ring and a preparation method and application thereof. In particular, the invention also provides a pharmaceutical composition comprising an effective amount of the derivative or pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier; moreover, the derivative or the pharmaceutically acceptable salt thereof can be used for treating inflammation-related diseases and has antitumor activity, and the safety of the compound is improved or equivalent.
- -
-
Paragraph 0087-0091
(2020/07/21)
-
- Aralia elata seem monomer saponin derivative and preparation method and use thereof
-
The invention discloses an aralia elata seem monomer saponin derivative and a preparation method and use thereof. The derivative has a structure represented by a general formula (I). Oleanolic acid orursolic acid, five kinds of sugars and caffeic acid are
- -
-
Paragraph 0119-0121
(2019/08/30)
-
- 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
-
-
- Semisynthesis and biological evaluation of oleanolic acid 3-O-β-D-Glucuronopyranoside derivatives for protecting H9c2 cardiomyoblasts against H2O2-Induced injury
-
A series of novel oleanolic acid 3-O-β-D-glucuronopyranoside derivatives have been designed and synthesized. Biological evaluation has indicated that some of the synthesized compounds exhibit moderate to good activity against H2O2-in
- Tian, Yu,Sun, Zhonghao,Wang, Wenqian,Shang, Hai,Wang, Baoqi,Deng, Di,Ma, Guoxu,Wu, Haifeng,Zhu, Nailiang,Xu, Xudong,Sun, Guibo,Sun, Xiaobo
-
-
- Targeting mitochondria: Esters of rhodamine B with triterpenoids are mitocanic triggers of apoptosis
-
Triterpenoic acids, ursolic acid (1), oleanolic acid (2), glycyrrhetinic acid (3) and betulinic acid (4) were converted into their corresponding methyl 5–8 and benzyl esters 9–12 or benzyl amides 21–24. These derivatives served as starting materials for the synthesis of pink colored rhodamine B derivatives 25–36 which were screened for cytotoxicity in colorimetric SRB assays. All of the compounds were cytotoxic for a variety of human tumor cell lines. The activity of the benzyl ester derivatives 29–32 was lower than the cytotoxicity of the methyl esters 25–28. The benzyl amides 33–36 were the most cytotoxic compounds of this series. The most potential compound was a glycyrrhetinic acid rhodamine B benzyl amide 35. This compound showed activity against the different cancer cell lines in a two-digit to low three-digit nano-molar range. Staining experiments combined with fluorescence microscopy showed that this compound triggered apoptosis in A2780 ovarian carcinoma cells and acted as a mitocan.
- Wolfram, Ratna Kancana,Heller, Lucie,Csuk, René
-
supporting information
p. 21 - 30
(2018/04/26)
-
- Design and preparation of derivatives of oleanolic and glycyrrhetinic acids with cytotoxic properties
-
Background: The structural modification of natural products with the aim to improve the anticancer activity is a popular current research direction. The pentacyclic triterpenoid compounds oleanolic acid (OA) and glycyrrhetinic acid (GA) are distributed widely in nature. Methods: In this study, various oleanolic acids and glycyrrhetinic acids were designed and synthesized by using the combination principle. The in vitro anticancer activities of new OA and GA derivatives were tested by the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) method with SGC-7901 (gastric cancer), MCF-7 (breast cancer), Eca-109 (esophageal cancer), HeLa (cervical cancer), Hep-G2 (hepatoma cancer) and HSF (normal human skin fibroblast) cells. Results and conclusion: The screening results showed that the compound 3m presented the highest inhibitory activities against SGC-7901, MCF-7 and Eca-109 cell lines with IC50 values of 7.57±0.64 μM, 5.51±0.41 μM and 5.03±0.56 μM, respectively. In addition, this compound also showed effective inhibition of Hep-G2 cells with an IC50 value of 4.11±0.73 μM. Moreover, compound 5b showed the strongest inhibitory activity against Hep-G2 cells with an IC50 value of 3.74±0.18 μM and compound 3l showed strong selective inhibition of the HeLa cells with the lowest IC50 value of 4.32±0.89 μM. A series of pharmacology experiments indicated that compound 5b could induce Hep-G2 cells autophagy and apoptosis. These compounds will expand the structural diversity of anti-cancer targets and confirm the prospects for further research.
- Wang, Rui,Li, Yang,Huai, Xu-Dong,Zheng, Qing-Xuan,Wang, Wei,Li, Hui-Jing,Huai, Qi-Yong
-
p. 1321 - 1336
(2018/06/06)
-
- 3 - monosaccharide acid oxygen glucoside oleanolic alkane type and wusu alkane triterpene saponin derivative and its preparation method and application
-
The invention discloses a 3-monouronic acid o-glycoside oleanane type and ursane type triterpenoid saponin derivative. The derivative has a structural formula as shown in the specification, wherein R4 is one of H atom, alkyl containing 1-10 carbons, alkyl
- -
-
Paragraph 0040; 0041
(2017/08/25)
-
- Discovery of pentacyclic triterpene 3β-ester derivatives as a new class of cholesterol ester transfer protein inhibitors
-
A series of pentacyclic triterpene 3β-ester derivatives were designed, synthesized and evaluated as a new class of cholesteryl ester transfer protein (CETP) inhibitors for the treatment of dyslipidemia. In vitro screening assay showed that 5 out of 30 compounds displayed moderate inhibiting human CETP activity with IC50s less than 10 μM. Among them, compound 20 (IC50 = 2.3 μM) had the most potent biological activity, and effectively ameliorated plasma lipid levels of human adipose tissue specific CETP transgenic (ap2-CETPTg) mice and guinea pigs. Additional safety evaluation (no blood pressure elevation in guinea pigs) and pharmacokinetics studies indicated that the potential druggability for compound 20 which is a promising lead for development of a new class of CETP inhibitors for the treatment of dyslipidemia.
- Chen, Dongyin,Huang, Xin,Zhou, Hongwen,Luo, Hanqiong,Wang, Pengfei,Chang, Yongzhi,He, Xinyi,Ni, Suiying,Shen, Qingqing,Cao, Guoshen,Sun, Hongbin,Wen, Xiaoan,Liu, Jun
-
p. 201 - 213
(2017/08/16)
-
- Triterpenoid derivative TBA-X with antitumor effect as well as preparation method and application thereof
-
The invention provides a compound with a structural general form 1 or 2, a preparation method thereof, and an application of the compound in preparation of antitumor drugs. The composition provided by the invention has a significant inhibitory action on liver cancer, stomach cancer, colon cancer, cervical cancer cell lines.
- -
-
Paragraph 0058; 0059; 0092; 0093; 0094
(2017/08/28)
-
- Fragment-based discovery of novel pentacyclic triterpenoid derivatives as cholesteryl ester transfer protein inhibitors
-
Cholesteryl Ester Transfer Protein (CETP) is an important therapeutic target for the treatment of atherosclerotic cardiovascular disease. Our molecular modeling study revealed that pentacyclic triterpenoid compounds could mimic the protein-ligand interactions of the endogenous ligand cholesteryl ester (CE) by occupying its binding site. Alignment of the docking conformations of oleanolic acid (OA), ursolic acid (UA) and the crystal conformations of known CETP inhibitor Torcetrapib in the active site proposed the applicability of fragment-based drug design (FBDD) approaches in this study. Accordingly, a series of pentacyclic triterpenoid derivatives have been designed and synthesized as novel CETP inhibitors. The most potent compound 12e (IC50:0.28?μM) validated our strategy for molecular design. Molecular dynamics simulations illustrated that the more stable hydrogen bond interaction of the UA derivative 12e with Ser191 and stronger hydrophobic interactions with Val198, Phe463 than those of OA derivative 12b mainly led to their significantly different CETP inhibitory activity. These novel potent CETP inhibitors based on ursane-type scaffold should deserve further investigation.
- Chang, Yongzhi,Zhou, Shuxi,Li, Enqin,Zhao, Wenfeng,Ji, Yanpeng,Wen, Xiaoan,Sun, Hongbin,Yuan, Haoliang
-
p. 143 - 153
(2016/10/25)
-
- Microbial hydroxylation and glycosylation of pentacyclic triterpenes as inhibitors on tissue factor procoagulant activity
-
To discover new inhibitors on tissue factor procoagulant activity, 20 pentacyclic triterpenes were semi-synthetized through microbial transformation and assayed on the model of human THP-1 cells stimulated by lipopolysaccharide. In the biotransformation two types of reactions were observed, regio-selective hydroxylation and glycosylation. The bioassay results showed that most of tested compounds were significant effective on this model and two of the biotransformation products 23-hydroxy-28-O-β-D-glucopyranosyl betulinic acid (3d) and 28-O-β-D-glucopyranosyl oleanic acid (1a) exhibited most potential activities with the IC50 values of 0.028, 0.035 nM respectively. The preliminary structure and activity relationship analysis revealed that the aglycones with single free hydroxyl group on the skeleton (1, 1j) were less effective than that with more free hydroxyl groups (1d, 1f, 2), mono-glycosylation can significantly enhance their inhibitory effects. Our findings also provide some potential leading compounds for tissue factor-related diseases, such as cancer and cardiovascular diseases.
- Wang, Wei-Wei,Xu, Shao-Hua,Zhao, Ya-Zheng,Zhang, Chao,Zhang, Yuan-Yuan,Yu, Bo-Yang,Zhang, Jian
-
p. 1026 - 1030
(2017/09/30)
-
- Discovery of Farnesoid X Receptor Antagonists Based on a Library of Oleanolic Acid 3-O-Esters through Diverse Substituent Design and Molecular Docking Methods
-
The pentacyclic triterpene oleanolic acid (OA, 1) with known farnesoid X receptor (FXR) modulatory activity was modified at its C-3 position to find new FXR-interacting agents. A diverse substitution library of OA derivatives was constructed in silico through a 2D fingerprint similarity cluster strategy. With further docking analysis, four top-scored OA 3-O-ester derivatives were selected for synthesis. The bioassay results indicated that all four compounds 3 inhibited chenodeoxycholic acid (CDCA)-induced FXR transactivation in a concentration-dependent mode. Among them 3b and 3d are more active than the parent compound OA. A molecular simulation study was performed to attempt to explain the structure-Activity relationship (SAR) and the antagonistic action. To the best of our knowledge, this is the first report on semi-synthetic pentacyclic triterpenoids with FXR-modulatory activities.
- Wang, Shao-Rong,Xu, Tingting,Deng, Kai,Wong, Chi-Wai,Liu, Jinsong,Fang, Wei-Shuo
-
supporting information
(2017/06/08)
-
- The oleanolic acid derivative, 3-: O -succinyl-28- O -benzyl oleanolate, induces apoptosis in B16-F10 melanoma cells via the mitochondrial apoptotic pathway
-
Oleanolic acid (1) is a pentacyclic triterpene present in olive pomace, which is known to induce apoptosis and to have anti-tumor properties; however, high concentrations of this product are necessary to produce cytotoxic effects. The 3-O-succinyl-28-O-benzyl oleanolate derivative (4) presents greater cytotoxicity and apoptosis effects than its natural precursor, oleanolic acid, or its benzyl derivative (2). This study examines the response of B16-F10 melanoma cells to treatment with compound 4, in comparison to 1 and 3. Our studies show that treatment with 4 results in a significant inhibition of cell proliferation in a dose-dependent manner and causes apoptotic cell death. At concentrations inhibiting cell growth by 50% and 80%, compound 4 induces strong G0/G1 cell-cycle arrest, around 72-95% apoptosis, and mitochondrial disturbances confirmed by FACS analysis, which probably involve the activation of the intrinsic apoptotic route. Morphological changes including cell shrinkage, chromatin condensation, and loss of nuclear architecture were also observed. In this report, we demonstrated for the first time that in melanoma cancer cells, compound 4 exerts a significant anti-proliferation effect by inducing the apoptotic process with mitochondrial depolarization. These findings support the role of compound 4 as a new, potential therapeutic tool against aberrant cell proliferation in melanoma.
- Reyes-Zurita, Fernando J.,Medina-O'Donnell, Marta,Ferrer-Martin, Rosa M.,Rufino-Palomares, Eva E.,Martin-Fonseca, Samuel,Rivas, Francisco,Martínez, Antonio,García-Granados, Andrés,Pérez-Jiménez, Amalia,García-Salguero, Leticia,Peragón, Juan,Mokhtari, Khalida,Medina, Pedro P.,Parra, Andrés,Lupiá?ez, José A.
-
p. 93590 - 93601
(2016/10/17)
-
- Synthesis and Biological Evaluation of Novel Olean-28,13β-lactams as Potential Antiprostate Cancer Agents
-
γ-Lactam is an important structural motif in a large number of biologically active natural products and synthetic small pharmaceutical molecules. However, there is currently no effective approach to construct γ-lactam ring directly from natural rigid polycyclic amides. Herein, we report a facile methodology for synthesis of a new group of olean-28,13β-lactams (10a-j) from their corresponding amides, promoted by an easily available reagent 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ), through an intramolecular dehydrogenative C-N coupling reaction via a radical ion mechanism. Biological evaluation indicated that the most active lactam 10h displayed potent antiproliferative activity against human cancer cells but 13.84- to 16.92-fold less inhibitory activity on noncancer cells in vitro. In addition, 10h significantly inhibited the growth of implanted prostate cancer in vivo. Furthermore, 10h induced cell cycle arrest and apoptosis and down-regulated the AKT/mTOR signaling in DU-145 cells. Finally, 10h was more stable in rat plasma and human liver microsomes than CDDO-Me and had little hERG channel inhibitory activity. Collectively, 10h may be a potential antiprostate cancer agent for further investigation.
- Ai, Yong,Hu, Yang,Kang, Fenghua,Lai, Yisheng,Jia, Yanju,Huang, Zhangjian,Peng, Sixun,Ji, Hui,Tian, Jide,Zhang, Yihua
-
p. 4506 - 4520
(2015/06/23)
-
- Synthesis of oxygenated oleanolic and ursolic acid derivatives with anti-inflammatory properties
-
The scalable syntheses of four oxygenated triterpenes have been implemented to access substantial quantities of maslinic acid, 3-epi-maslinic acid, corosolic acid, and 3-epi-corosolic acid. Semi-syntheses proceed starting from the natural products oleanolic acid and ursolic acid. Proceeding over five steps, each of the four compounds can be synthesized on the gram scale. Divergent diastereoselective reductions of α-hydroxy ketones provided access to the four targeted diol containing compounds from two precursors of the oleanane or ursane lineage. These compounds were subsequently evaluated for their ability to inhibit inflammatory gene expression in a mouse model of chemically induced skin inflammation. All compounds possessed the ability to inhibit the expression of one or more inflammatory genes induced by 12-O-tetradecanoylphorbol-13 acetate in mouse skin, however, three of the compounds, corosolic acid, 3-epi-corosolic acid and maslinic acid were more effective than the others. The availability of gram quantities will allow further testing of these compounds for potential anti-inflammatory activities as well as cancer chemopreventive activity.
- Nelson, Andrew T.,Camelio, Andrew M.,Claussen, Karin R.,Cho, Jiyoon,Tremmel, Lisa,Digiovanni, John,Siegel, Dionicio
-
p. 4342 - 4346
(2015/11/03)
-
- Synthesis and biological evaluation of Raddeanin A, a triterpene saponin isolated from Anemone raddeana
-
First, Raddeanin A, a cytotoxic oleanane-type triterpenoid saponin isolated from Anemone raddeana REGEL, was synthesized. Stepwise glycosylation was adopted in the synthesis from oleanolic acid, employing arabinosyl, glucosyl and rhamnosyl trichloroacetimidate as donors. The chemical structure of Raddeanin A was confirmed by means of 1H-NMR, 13C-NMR, IR, MS and elemental analysis, which elucidated the structure to be 3-O-α-L-rhamnopyranosyl-(1→2)-β-D-glucopyranosyl-(1→2)-α-L-arabinopyranoside oleanolic acid. Biological activity tests showed that in the range of low concentrations, Raddeanin A displayed moderate inhibitory activity against histone deacetylases (HDACs), indicating that the HDACs' inhibitory activity of Raddeanin A may contribute to its cytotoxicity.
- Qian, Shan,Chen, Quan Long,Guan, Jin Long,Wu, Yong,Wang, Zhou Yu
-
p. 779 - 785
(2016/10/12)
-
- Towards cytotoxic and selective derivatives of maslinic acid
-
Several novel esters and amides of maslinic acid were prepared. Their evaluation for cytotoxic activity with a panel of human cancer cell lines using a sulforhodamine B (SRB) assay revealed for some of them a noteworthy activity. The results from annexinV-FITC and caspase-assays as well as from DNA laddering experiments provided evidence for an apoptotic cell death. A diacetylated benzylamide (15) induced a G1/G0 arrest in tumor cells. It also displayed an extraordinary cytotoxicity against human ovarian cancer cells but a 300 times lower toxicity for non-malignant primary human fibroblasts.
- Siewert, Bianka,Pianowski, Elke,Obernauer, Anja,Csuk, René
-
p. 594 - 615
(2014/01/17)
-
- Novel inhibitors of bacterial biofilms and related methods
-
Multi-cyclic compounds of chemical structure represented by formula given below and compositions thereof are useful for reducing or inhibiting the growth of bacterial biofilms and for controlling bacterial biofilm infections. Such compounds and compositions are also useful in methods for reducing or inhibiting the growth of biofilms and for controlling bacterial biofilm infections involving biofilms.
- -
-
Paragraph 0192; 0193
(2014/05/06)
-
- Synthesis and evaluation of the anticancer activity of albiziabioside A and its analogues as apoptosis inducers against human melanoma cells
-
We have efficiently synthesized albiziabioside A (1) together with its six disaccharide analogues through a linear synthesis, and evaluated their cytotoxicity against six different skin cancer cells. All of the analogues showed weak cytotoxicity, with the
- Liu, Yang,Wei, Gaofei,Wang, Shuai,Cui, Shanshan,Guo, Jia,Liu, Yongxiang,Cheng, Maosheng
-
p. 5928 - 5935
(2014/08/05)
-
- Proton-exchanged montmorillonite-mediated reactions of methoxybenzyl esters and ethers
-
Proton-exchanged montmorillonite (H-mont) was found to be an eco-friendly and cost-effective catalyst for the generation of O-methylated quinone methides (QM) from the corresponding p or o-methoxybenzyl esters and ethers. Nucleophilic trapping of the O-methylated QM with arenes, alcohols, 1,3-dicarbonyl compounds, silyl enol ethers, and allylsilanes has been carried out, respectively, leading to eco-friendly benzylation reactions. Using this protocol, H-mont-mediated deprotection of PMB-protected esters and ethers have been realized for the first time. This work would pave the way for further exploration in O-alkylated QM that are of chemical and biological significance.
- Chen, Dongyin,Xu, Chang,Deng, Jie,Jiang, Chunhuan,Wen, Xiaoan,Kong, Lingyi,Zhang, Ji,Sun, Hongbin
-
p. 1975 - 1983
(2014/03/21)
-
- Semi-synthesis of acylated triterpenes from olive-oil industry wastes for the development of anticancer and anti-HIV agents
-
A broad set of potential bioactive conjugate compounds has been semi-synthesized through solution- and solid-phase organic procedures, coupling two natural pentacyclic triterpene acids, oleanolic (OA) and maslinic acids (MA), at the hydroxyl groups of the A-ring of the triterpene skeleton, with 10 different acyl groups. These acyl OA and MA derivatives have been tested for their anti-proliferative (against the b16f10 murine melanoma cancer cells) and antiviral (as inhibitors of the HIV-1-protease) effects. Several derivatives have shown high levels of early and total apoptosis (up to 90%). Most of the compounds that exhibited anti-proliferative effects also generated ROS, probably involving the activation of an intrinsic apoptotic route. The only four compounds that did not cause the release of ROS could be related to the participation of a probable extrinsic activation of the apoptosis mechanism. A great number of these acyl OA and MA derivatives have proved to be potent inhibitors of the HIV-1-protease, the most active inhibitors having IC 50 values between 0.31 and 15.6 μM, these values being between 4 and 186 times lower than their non-acylated precursors. The potent activities exhibited in the apoptosis-activation processes and in the inhibition of the HIV-1-protease by some OA and MA acylated derivatives imply that these compounds could be used as new, safe, and effective anticancer and/or antiviral drugs.
- Parra, Andres,Martin-Fonseca, Samuel,Rivas, Francisco,Reyes-Zurita, Fernando J.,Medina-O'Donnell, Marta,Martinez, Antonio,Garcia-Granados, Andres,Lupia?ez, Jose A.,Albericio, Fernando
-
p. 278 - 301
(2014/02/14)
-
- The chemical and biological potential of C ring modified triterpenoids
-
A convenient and elegant route has been developed to separate the natural regioisomers triterpenoids ursolic acid (UA) and oleanolic acid (OA) as well as derivatives thereof. Eleven unknown derivatives of OA were designed, synthesized, and their cytotoxicity was investigated. Further sixteen compounds were prepared to correlate all compounds in a SAR study. It could be shown that C-ring modifications of OA and UA have only a moderate influence onto the cytotoxic activity of the compounds but a significant impact onto the ability to trigger apoptosis in ovarian cancer cells (cell line A2780).
- Siewert, Bianka,Wiemann, Jana,K?witsch, Alexander,Csuk, René
-
-
- Synthesis of oleanolic acid derivatives: In vitro, in vivo and in silico studies for PTP-1B inhibition
-
Non-insulin dependent diabetes mellitus is a multifactorial disease that links different metabolic routes; a point of convergence is the enzyme PTP-1B which turns off insulin and leptin receptors involved in glucose and lipid metabolism, respectively. Pentacyclic acid triterpenes such as oleanolic acid (OA) have proved to be excellent PTP-1B inhibitors, thus, the purpose of current work was to generate a series of derivatives that improve the pharmacological effect of OA. Our findings suggest that the presence of the carboxylic acid and/or its corresponding reduction product carbinol derivative (H-bond donor) in C-28 is required to maintain the inhibitory activity; moreover, this is further enhanced by ester or ether formation on C-3. The most active derivatives were cinnamoyl ester (6) and ethyl ether (10). Compound 6 showed potent in vitro inhibitory activity and significantly decrease of blood glucose levels on in vivo experiments. Meanwhile, 10 showed contrasting outcomes, since it was the compound with higher inhibitory activity and selectivity over PTP-1B and has improved interaction with site B, according with docking studies, the in vivo antidiabetic effect was similar to oleanolic acid. In conclusion, oleanolic acid derivatives have revealed an enhanced inhibitory effect over PTP-1B activity by increasing molecular interactions with either catalytic or allosteric sites and producing a hypoglycaemic effect on non insulin dependent diabetes mellitus rat model.
- Ramírez-Espinosa, Juan José,Rios, Maria Yolanda,Paoli, Paolo,Flores-Morales, Virginia,Camici, Guido,Rosa-Lugo, Vianey De La,Hidalgo-Figueroa, Sergio,Navarrete-Vázquez, Gabriel,Estrada-Soto, Samuel
-
p. 316 - 327
(2015/02/19)
-
- Synthesis and evaluation of novel oleanolic acid derivatives as potential antidiabetic agents
-
Antidiabetic agents simultaneously inhibiting hepatic glucose production and stimulating hepatic glucose consumption could apply a better control over hyperglycemia. A series of oleanolic acid derivatives with bulky substituents at C-3 position were designed and synthesized in order to search for this kind of agents. All of the compounds were evaluated biologically in vitro using glycogen phosphorylase and HepG2 cells. The results indicated that several derivatives exhibited moderate-to-good inhibitory activities against glycogen phosphorylase. Compound 8g showed the best inhibition with an IC50 value of 5.4 μm. Moreover, most of the derivatives were found to increase the glucose consumption in HepG2 cells in a dose-dependent manner. The possible binding mode of compound 8g with glycogen phosphorylase was also explored by docking study. 8g was found to have hydrogen bonding interactions with Arg193, Arg310, and Arg60 of the allosteric site.
- Zhang, Liying,Jia, Xiaojian,Dong, Jizhe,Chen, Dongyin,Liu, Jun,Zhang, Luyong,Wen, Xiaoan
-
p. 297 - 305
(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 0114-0115
(2014/10/16)
-
- Synthesis and cytotoxicity evaluation of oleanolic acid derivatives
-
Twelve derivatives of oleanolic acid (1) have been synthesized and evaluated for their inhibitory activities against the growth of prostate PC3, breast MCF-7, lung A549, and gastric BGC-823 cancer cells by MTT assays. Within these series of derivatives, compound 17 exhibited the most potent cytotoxicity against PC3 cell line (IC50 = 0.39 μM) and compound 28 displayed the best activity against A549 cell line (IC50 = 0.22 μM). SAR analysis indicates that H-donor substitution at C-3 position of oleanolic acid may be advantageous for improvement of cytotoxicity against PC3, A549 and MCF-7 cell lines.
- Hao, Jia,Liu, Jun,Wen, Xiaoan,Sun, Hongbin
-
p. 2074 - 2077
(2013/04/23)
-
- Design, synthesis, and biological evaluation of potent photoaffinity probes of oleanolic acid
-
To study the target proteins of oleanolic acid, a series of novel photoaffinity probes were designed and synthesized. Their affinity for the target proteins was evaluated in an enzyme inhibition assay against glycogen phosphorylase, a known target protein of oleanolic acid. Among these compounds, probe 2 exhibited the most potent activity with an IC50value of 5.98 μM, which was about 2.5-fold more potent than its parent compound oleanolic acid. The results showed that the synthesized photoaffinity probes retained the binding affinity for their target proteins, and might be used as powerful tools to fish out the target proteins of oleanolic acid.
- Zhang, Liying,Dong, Jizhe,Zhang, Yingxia,Liu, Jun,Zhang, Luyong,Sun, Hongbin
-
p. 294 - 302
(2013/07/28)
-
- An efficient and recyclable catalyst for the cleavage of tert-butyldiphenylsilyl ethers
-
An efficient, chemoselective, and environment-friendly method for the deprotection of tert-butyldiphenylsilyl ethers mediated by triflic acid supported on silica gel is reported. A wide range of tert-butyldiphenylsilyl ethers derived from carbohydrate and saponin residues can be smoothly cleaved in the presence of various types of other protecting groups in good to excellent yields in acetonitrile. This heterogeneous reaction does not require aqueous workup, and the supported catalyst can be readily recycled.
- Yan, Shiqiang,Ding, Ning,Zhang, Wei,Wang, Peng,Li, Yingxia,Li, Ming
-
experimental part
p. 6 - 20
(2012/07/13)
-
- Synthesis and biological evaluation of oleanolic acid derivatives as novel inhibitors of protein tyrosine phosphatase 1B
-
A series of oleanolic acid (OA) derivatives have been synthesized and their inhibitory effects on PTP1B, TCPTP and related PTPs are evaluated. Some compounds with five-membered heterocyclic ring-fused at C-2, C-3 positions showed a dramatic increase in in
- Li, Hui,Zou, Hui,Gao, Lixin,Liu, Ting,Yang, Fan,Li, Jingya,Li, Jia,Qiu, Wen-Wei,Tang, Jie
-
experimental part
p. 1117 - 1139
(2012/08/07)
-
- Facile synthesis of triterpenoid saponins bearing β-Glu/Gal-(1→3) -β-GluA methyl ester and their cytotoxic activities
-
Convenient synthetic strategy toward spinasaponin A methyl ester 1 and calenduloside G methyl ester 2, two natural oleanane-type triterpenoid saponins bearing an unique β-d-glucosyl/galactosyl-(1→3)-β-d-glucuronic acid methyl ester disaccharide moiety, was established. Based on this facile approach, four structurally modified congeners 3-6 with ursolic acid and glycyrrhetinic acid as aglycones were efficiently synthesized. MTT assay revealed the cytotoxicities against cancer cells of the synthesized saponins were varied with the change of aglycones and sugar units. Saponin 2 possessing the most potent cytotoxic effects could induce apoptosis of MCF-7 cells, which was detected by confocal micrographs using DAPI staining and flow cytometry using Annexin V and PI double staining. Furthermore, 2-induced apoptosis in MCF-7 cells was associated with ROS generation and loss of the mitochondria membrane potential (Δψm).
- Gao, Jian,Li, Xia,Gu, Guofeng,Liu, Shanshan,Cui, Min,Lou, Hong-Xiang
-
supporting information; experimental part
p. 2396 - 2400
(2012/05/19)
-
- Design and synthesis of novel photoaffinity probes for study of the target proteins of oleanolic acid
-
To explore the molecular mechanisms of oleanolic acid, two novel photoaffinity probes were synthesized based on the structure-activity relationship reported previously. Their potency were evaluated in an enzyme inhibition assay against rabbit muscle glycogen phosphorylase a (RMGPa), a known target protein of oleanolic acid. The inhibitory activity of probe 2 was only about two-fold less potent than the mother compound oleanolic acid. The photoaffinity labeling experiments were also performed and two proteins were specifically tagged by probe 2. The results suggest that the synthesized probes could be used as powerful tools to isolate and identify the target proteins of oleanolic acid.
- Zhang, Liying,Zhang, Yingxia,Dong, Jizhe,Liu, Jun,Zhang, Luyong,Sun, Hongbin
-
scheme or table
p. 1036 - 1039
(2012/03/26)
-
- Efficient and selective removal of chloroacetyl group promoted with tetra-n-butylammonium fluoride (TBAF)
-
A practical method for the efficient and selective cleavage of chloroacetyl protecting group using tetra-n-butylammonium fluoride (TBAF) in THF solution at rt was disclosed.
- Gu, Guofeng,Fang, Min,Du, Yuguo
-
experimental part
p. 2801 - 2804
(2012/01/02)
-
- MODIFIED C-3 BETULINIC ACID DERIVATIVES AS HIV MATURATION INHIBITORS
-
Compounds having drug and bio-affecting properties, their pharmaceutical compositions and methods of use are set forth. In particular, modified C-3 betulinic acid and other structurally related natural products derivatives that possess unique antiviral activity are provided as HIV maturation inhibitors. These compounds are useful for the treatment of HIV and AIDS.
- -
-
Page/Page column 111; 112
(2011/12/14)
-
- C-28 AMIDES OF MODIFIED C-3 BETULINIC ACID DERIVATIVES AS HIV MATURATION INHIBITORS
-
Compounds having drug and bio-affecting properties, their pharmaceutical compositions and methods of use are set forth. In particular, modified C-3 and C-28 betulinic acid derivatives that possess unique antiviral activity are provided as HIV maturation inhibitors. These compounds are useful for the treatment of HIV and AIDS.
- -
-
Page/Page column 246
(2011/12/14)
-
- Identification of pentacyclic triterpenes derivatives as potent inhibitors against glycogen phosphorylase based on 3D-QSAR studies
-
Naturally occurring pentacyclic triterpenes (PT), a novel class of inhibitors against glycogen phosphorylase (GP), hold promise for the treatment of type-2 diabetes and other diseases with disorders in glycogen metabolism. To identify novel and more potent GP inhibitors, the receptor-based comparative molecular field analysis (CoMFA) and comparative molecular similarity analysis (CoMSIA) approaches were performed to investigate the quantitative structure-activity relationships (QSAR) among 106 PT analogues. The validated models demonstrated that the elongated or bulky substitutions in C17 position and/or C2, C3 positions are favorable. Then based on the structural information extracted from these models, 56 derivatives were synthesized and biochemically tested in this study. The IC50 value of the most potent compound P50 was found to be 1.1 μM.
- Liang, Zhongjie,Zhang, Liying,Li, Lianchun,Liu, Jun,Li, Hongling,Zhang, Luyong,Chen, Limin,Cheng, Keguang,Zheng, Mingyue,Wen, Xiaoan,Zhang, Pu,Hao, Jia,Gong, Yanchun,Zhang, Xia,Zhu, Xiaoyun,Chen, Jun,Liu, Hong,Jiang, Hualiang,Luo, Cheng,Sun, Hongbin
-
supporting information; experimental part
p. 2011 - 2021
(2011/06/22)
-
- Synthesis and tumor cytotoxicity of novel amide derivatives of β-hederin
-
Thirteen novel triterpenoid saponins, designed as amide derivatives of the natural cytotoxic saponin α-hederin, were synthesized by a stepwise glycosylation strategy. The in vitro cytotoxic activity of these compounds was evaluated against five different
- Liu, Yang,Lu, Wen-Xiang,Yan, Mao-Cai,Yu, Yang,Ikejima, Takashi,Cheng, Mao-Sheng
-
experimental part
p. 7871 - 7883
(2011/03/21)
-
- Synthesis and α-glucosidase inhibitory activity of oleanolic acid derivatives
-
Glucosidations of oleanolic acid (1) and its dihydroxy-olide derivatives (2) were carried out to provide eight glycosides. All synthesized compounds were evaluated by in vitro α-glucosidase inhibitory activity assay. 3-Acetyl dihydroxy-olide oleanolic der
- Qian, Shan,Hai Li, Jiao,Wei Zhang, Yu,Chen, Xin,Wu, Yong
-
scheme or table
p. 20 - 29
(2010/09/18)
-
- Synthesis and biological evaluation of heterocyclic ring-substituted maslinic acid derivatives as novel inhibitors of protein tyrosine phosphatase 1B
-
A series of maslinic acid derivatives have been synthesized by introducing various fused heterocyclic rings at C-2 and C-3 positions. Their inhibitory effects on PTP1B, TCPTP and related PTPs are evaluated. Most of the compounds exhibited a dramatic increase in inhibitory potency and selectivity, the two most potent PTP1B inhibitors 20 (IC50 = 0.61 μM) and 29 (IC50 = 0.64 μM) showed about 10-fold more potent than lead compound maslinic acid. More importantly, 29 possesses the best selectivity of 6.9-fold for PTP1B over TCPTP.
- Qiu, Wen-Wei,Shen, Qiang,Yang, Fan,Wang, Bo,Zou, Hui,Li, Jing-Ya,Li, Jia,Tang, Jie
-
scheme or table
p. 6618 - 6622
(2010/06/12)
-
- Facile synthesis of oleanolic acid monoglycosides and diglycosides
-
Oleanolic acid and its glycosides are important natural products, possessing various attractive biological activities such as antitumor, antivirus and anti-inflammatory properties. In the present work, fifteen oleanolic acid saponins bearing various sacch
- Sha, Yu,Yan, Mao-Cai,Liu, Jiao,Liu, Yang,Cheng, Mao-Sheng
-
p. 1472 - 1486
(2008/12/21)
-
- Total synthesis of lobatoside E, A potent antitumor cyclic triterpene saponin
-
Lobatoside E, a novel and complex cyclic triterpene saponin showing potent antitumor activities, has been synthesized for the first time, employing a highly modular approach. The synthesis, starting with oleanolic acid, d-glucose, d-galactose, l-arabinose
- Zhu, Chunsheng,Tang, Pingping,Yu, Biao
-
p. 5872 - 5873
(2008/09/20)
-
- 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)
-
- Naturally occurring pentacyclic triterpenes as inhibitors of glycogen phosphorylase: Synthesis, structure-activity relationships, and X-ray crystallographic studies
-
Twenty-five naturally occurring pentacyclic triterpenes, 15 of which were synthesized in this study, were biologically evaluated as inhibitors of rabbit muscle glycogen phosphorylase a (GPa). From SAR studies, the presence of a sugar moiety in triterpene saponins resulted in a markedly decreased activity (7, 18-20) or no activity (21, 22). These saponins, however, might find their value as potential natural prodrugs which are much more water-soluble than their corresponding aglycones. To elucidate the mechanism of GP inhibition, we have determined the crystal structures of the GPb-asiatic acid and GPb-maslinic acid complexes. The X-ray analysis indicates that the inhibitors bind at the allosteric activator site, where the physiological activator AMP binds. Pentacyclic triterpenes represent a promising class of multiple-target antidiabetic agents that exert hypoglycemic effects, at least in part, through GP inhibition.
- Wen, Xiaoan,Sun, Hongbin,Liu, Jun,Cheng, Keguang,Zhang, Pu,Zhang, Liying,Hao, Jia,Zhang, Luyong,Ni, Peizhou,Zographos, Spyros E.,Leonidas, Demettes D.,Alexacou, Kyra-Melinda,Gimisis, Thanasis,Hayes, Joseph M.,Oikonomakos, Nikos G.
-
experimental part
p. 3540 - 3554
(2009/04/07)
-