- Water-induced gel formation of an oleanlic acid-adenine conjugate and the effects of uracil derivative on the gel stability
-
The conjugate of oleanlic acid with adenine was synthesized and it could be gelled in mixed solvents of THF and water, but no gel was formed in the single organic solvent. The self-aggregation behaviour and physical properties of the organogel were characterized by 1H NMR, FT-IR, and scanning electron microscopy. The morphology and the stability of the gel were remarkably affected by the uracil derivative through destroying hydrogen-bonding.
- Lu, Jinrong,Hu, Jun,Liu, Chulong,Gao, Hongxin,Ju, Yong
-
-
Read Online
- Protein tyrosine phosphatase 1B inhibitory activity of triterpenes isolated from Astilbe koreana
-
Bioassay-guided fractionation of a MeOH extract of the rhizomes of Astilbe koreana (Saxifragaceae), using an in vitro protein tyrosine phosphatase 1B (PTP1B) inhibitory assay, resulted in the isolation of a new triterpene, 3α,24-dihydroxyolean-12-en-27-oic acid (4), along with four triterpenes, 3-oxoolean-12-en-27-oic acid (1), 3β-hydroxyolean-12-en-27-oic acid (β-peltoboykinolic acid; 2), 3β-hydroxyurs-12-en-27-oic acid (3), and 3β,6β-dihydroxyolean-12-en-27-oic acid (astilbic acid; 5). Compounds 1-5 inhibited PTP1B with IC50 values of 6.8 ± 0.5, 5.2 ± 0.5, 4.9 ± 0.4, 11.7 ± 0.9, and 12.8 ± 1.1 μM, respectively. Our results indicate that 3-hydroxyl group and a carboxyl group in this type of triterpenes may be required for the activity, while addition of one more hydroxyl group at C-6 or C-24 may be responsible for a loss of activity. Thus, compounds 2 and 3 which possess only one hydroxyl group at C-3 and a carboxyl group at C-27 could be potential PTP1B inhibitors.
- Na, MinKyun,Cui, Long,Min, Byung Sun,Bae, KiHwan,Yoo, Jae Kuk,Kim, Bo Yeon,Oh, Won Keun,Ahn, Jong Seog
-
-
Read Online
- 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).
- Umehara,Takagi,Kuroyanagi,Ueno,Taki,Chen
-
-
Read Online
- Efficient and scalable synthesis of bardoxolone methyl (CDDO-methyl ester)
-
Bardoxolone methyl (2-cyano-3,12-dioxooleane-1,9(11)-dien-28-oic acid methyl ester; CDDO-Me) (1), a synthetic oleanane triterpenoid with highly potent anti-inflammatory activity (levels below 1 nM), has completed a successful phase I clinical trial for the treatment of cancer and a successful phase II trial for the treatment of chronic kidney disease in type 2 diabetes patients. Our synthesis of bardoxolone methyl (1) proceeds in ～50% overall yield in five steps from oleanolic acid (2), requires only one to two chromatographic purifications, and can provide gram quantities of 1.
- Fu, Liangfeng,Gribble, Gordon W.
-
-
Read Online
- TWO SAPONINS FROM ZEXMENIA BUPHTHALMIFLORA
-
Oleanolic acid 3-O-(3'-O-α-L-rhamnopyranosyl)-β-D-glucuronopyranoside and its 28-O-β-D-glucopyranosyl ester have been isolated from aerial parts of Zexmenia buphthalmiflora.The chemotaxonomical significance of the transfer of Wedelia buphthalmiflora to Zexmenia buphthalmiflora is discussed. Key Word Index - Zexmenia buphthalmiflora; Wedelia buphthalmiflora; Heliantheae; Compositae; structure elucidation; saponins; oleanolic acid 3-O-(3'-O-α-L-rhamnopyranosyl)-β-D-glucopyranoside; oleanolic acid 3-O-(3'-O-α-L-rhamnopyranosyl)-β-D-glucuronopyranoside-28-O-β-D-glucopyranoside.
- Schteingart, Claudio D.,Pomilio, Alicia B.
-
-
Read Online
- Partial synthesis of krukovines A and B, triterpene ketones isolated from the Brazilian medicinal plant Maytenus krukovii
-
Krukovines A (1) and B (2), triterpene ketones isolated from the Brazilian medicinal plant 'chuchuhuasi' (Maytenus krukovii), were synthesized in eight steps from the commercially available oleanolic acid and ursolic acid, respectively.
- Honda,Finlay,Gribble
-
-
Read Online
- Synthesis and anion recognition of a novel oleanolic acid-based cyclic dimer
-
A novel cyclic dimer based on oleanolic acid was synthesized using click chemistry and it showed remarkable selectivity and affinity to bind fluoride ion through C-H...F hydrogen bond interactions which involved the delocalization of proton in methylene.
- Hu, Jun,Li, Ruofan,Lu, Jinrong,Ju, Yong
-
-
Read Online
- NEO-CLERODANE DITERPENOIDS FROM BACCHARIS MACRAEI
-
Key Word Index - Baccharis macraei; Compositae; diterpenes; neo-clerodanes. From the aerial parts of Baccharis macraei two new clerodane diterpenes, bacchasmacranone and 2β-hydroxybacchasmacranone, were isolated besides the known hardwickiic and hautriwaic acids.The structures of the new compounds were elucidated by spectroscopic methods.
- Gambaro, Vicente,Chamy, Maria C.,Garbarino, Juan A.,San-Martin, Aurelio,Castillo, Mariano
-
-
Read Online
- Biotransformation of oleanolic and maslinic methyl esters by Rhizomucor miehei CECT 2749
-
The pentacyclic triterpenoids methyl oleanolate, methyl maslinate, methyl 3β-hydroxyolean-9(11),12-dien-28-oate, and methyl 2α,3β-dihydroxy-12β,13β-epoxyolean-28-oate were biotransformed by Rhizomucor miehei CECT 2749. Microbial transformation of methyl oleanolate produced only a 7β,30-dihydroxylated metabolite with a conjugated 9(11),12-diene system in the C ring. Biotransformation of the substrate with this 9(11),12-diene system gave the same 7β,30-dihydroxylated compound together with a 7β,15α,30-trihydroxyl derivative. The action of this fungus (R. miehei) on methyl maslinate was more varied, isolating metabolites with a 30-hydroxyl group, a 9(11),12-diene system, an 11-oxo group, or an 12-oxo group. Microbial transformation of the substrate with a 12β,13β-epoxy function resulted in the isolation of two metabolites with 12-oxo and 28,13β-olide groups, hydroxylated or not at C-7β, together with a 30-hydroxy-12-oxo derivative. The structures of these derivatives were deduced by extensive and rigorous spectroscopic studies.
- Martinez, Antonio,Perojil, Alberto,Rivas, Francisco,Parra, Andres,Garcia-Granados, Andres,Fernandez-Vivas, Antonia
-
-
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
-
-
- Pentacylic triterpenes from Lavandula coronopifolia: structure related inhibitory activity on α-glucosidase
-
Ten pentacyclic triterpenes (1-10) were isolated from Lavandula coronopifolia. We evaluated their α-glucosidase inhibitory activity, and found that the aglycones, 1, 2, 3, 4, 7 and 10 showed superior IC50 values to the positive control. In order to explain the structural requirements for α-glucosidase inhibitory activity, eleven derivatives were prepared, including one new compound, 2-formyl-(A)1–19α-hydroxy-1-norursane-2, 12-dien-28-oic acid 10c. The results demonstrated that a free hydroxyl at ring-A and a free carboxylic group at position 28 are key structural features for the α-glucosidase inhibitory activity, also that an ursane skeleton is optimum for the activity. Additionally, enzyme kinetic analysis of pomolic acid 2, the most potent compound, revealed that it inhibited α-glucosidase in a mixed-type manner. The molecular docking simulation validated this type of inhibition and highlighted the role of the C-3 hydroxyl and C-28 carboxylic groups in interaction with the enzyme in silico.
- Elsbaey, Marwa,Mwakalukwa, Rogers,Shimizu, Kuniyoshi,Miyamoto, Tomofumi
-
p. 1436 - 1444
(2019/08/26)
-
- Application of methylsulfonyl 12-ketone oleanolic acid methyl ester in preparation of medicine for resisting viral hepatitis B
-
The invention relates to application of methylsulfonyl 12-ketone oleanolic acid methyl ester in preparation of a medicine for resisting viral hepatitis B, and particularly provides application of 3 beta-methylsulfonyloxy-12-carbonyl oleanane-28-carboxylic acid methyl ester in preparation of a medicine for preventing and treating hepatitis B virus infection diseases. The compound has remarkable activity of inhibiting HBsAg and HBeAg secreted by HepG2.2.15 cells. On the eighth day, the intensity of the compound at a concentration of 100 micrograms/milliliter for inhibiting the HBeAg secretion ishigher than that of positive control drugs alpha-interferon and lamivudine. The HBsAg secretion inhibition strength of the compound is 69.9% at the concentration, and the inhibition rate on HBV-DNA replication is higher than 97%. The above results show that the methylsulfonyl 12-ketone oleanolic acid methyl ester can be expected to be used for preparing non-nucleoside drugs for treating hepatitisB virus infection diseases. Specifically, the compound has the application for preparing an HBV-DNA inhibitor, an HBsAg inhibitor and an HBeAg inhibitor; and the preparation method is simple in steps, low in cost, wide in raw material source and easy for industrial production.
- -
-
Paragraph 0029-0030; 0034-0035
(2020/10/30)
-
- Application of methyl isocycloenone oleanolate to preparation of medicine for preventing and treating viral hepatitis B
-
The invention relates to an application of methyl isocycloenone oleanolate to preparation of a medicine for preventing and treating viral hepatitis B, and particularly provides an application of 3 beta-hydroxyl-12-carbonyl oleanane-13 (18)-alkene-28-carboxylic acid methyl ester to preparation of a medicine for resisting hepatitis B virus infection diseases. A compound has remarkable effect of inhibiting the activity of HBsAg and HBeAg secreted by HepG2.2. 15 cells, the intensity of inhibiting HBsAg and HBeAg secretion at the concentration of 100 micrograms/milliliter on the eighth day exceedsthat of positive control medicines namely alpha-interferon and lamivudine, and the inhibition rate of the compound on HBV-DNA replication is higher than 97% under the concentration. The result shows that the methyl isocycloenone oleanolate can be expected to be used for preparing non-nucleoside medicines for treating hepatitis B virus infection diseases; and specifically, the compound has the functions of being used for preparing an HBV-DNA inhibitor, an HBsAg inhibitor and an HBeAg inhibitor, and the preparation method is simple in step, low in cost, wide in raw material source and easy for industrial production.
- -
-
Paragraph 0029; 0032-0033
(2020/11/23)
-
- Medicinal application of 12-ketone methyl oleanolate in preparation of anti-viral hepatitis B medicine
-
The invention relates to medicinal application of 12-ketone methyl oleanolate in preparation of anti-viral hepatitis B medicines and particularly provides application of 3beta-hydroxyl-12-carbonyl oleanolate-28-methyl carboxylate in preparation of medicines for preventing and treating hepatitis B viral infectious diseases. The compound has remarkable activity of inhibiting HBsAg and HBeAg secreted from HepG2.2.15 cells, the strength of the compound on inhibiting secretion of HBsAg and HBeAg are respectively 89.1 percent and 95.1 percent under the concentration of 100mg/ml on the 8th day, replication of the compound on HBV-DNA can show the inhibition rate of 92.6 percent under the concentration of 100mg/ml, which is higher than that of positive medicines alpha-interferon. Thus, the 12-ketone methyl oleanolate is expected to be applied to preparation of non-nucleoside drugs for treating hepatitis B viral infectious diseases, especially applied to preparation of HBV-DNA inhibitors, HBsAginhibitors and HBeAg inhibitors. The preparation method has simple steps and low cost, is wide in raw material sources and is easy for industrial production.
- -
-
Paragraph 0032; 0033
(2020/11/23)
-
- Preparation of dienyl mesyloxy oleanane alcohol and medical application of dienyl mesyloxy oleanane alcohol in resisting hepatitis B
-
The invention relates to preparation of dienyl mesyloxy oleanane alcohol and a medical application of the dienyl mesyloxy oleanane alcohol in resisting hepatitis B. Particularly, the invention provides an application of 3[beta]-mesyloxy oleanane 11,13(18)-dien-28-ol in preparation of a medicine for preventing and treating hepatitis B virus infected diseases. The intensity of the compound for inhibiting the secretion of HBsAg and HBeAg under the concentration of 100 micrograms/milliliter exceeds that of positive drugs alpha-interferon and lamivudine; and when the test concentration is only 1/50(2.0 micrograms/milliliter) of the highest test concentration of the lamivudine, the inhibitory activity of the compound on HBV-DNA replication is as high as 44.1%. It is showed that the dienyl mesyloxy oleanane alcohol can be expected to be used for preparing non-nucleoside medicines for treating the hepatitis B virus infected diseases; specifically, the compound has an application for preparingan HBV-DNA inhibitor, an HBsAg inhibitor and an HBeAg inhibitor; and the preparation method is simple in steps, low in cost, wide in raw material source and easy for industrial production.
- -
-
Paragraph 0029; 0031; 0033; 0034
(2020/11/22)
-
- Total syntheses of (+)-arisugacins F, G
-
(+)-Arisugacin F and G are synthesized from commercially available oleanolic acid in 9 and 10 steps, respectively. This strategy features a AgOTf/Pd(PPh3)4-mediated cis/trans olefin isomerization and a highly convergent formal oxa-[3 + 3] cycloaddition between key α, β-unsaturated aldehyde and pyrone, which lays the foundation for efficient and concise synthesis of other natural products with similar terpenoid scaffolds.
- Chen, Ping,Li, Yu,Tang, Yu,Wu, Hao
-
supporting information
(2020/07/20)
-
- The Novel Synthetic Triterpene Methyl 3β-O-[4-(2-Aminoethylamino)-4-oxo-butyryl]olean-12-ene-28-oate Inhibits Breast Tumor Cell Growth in Vitro and in Vivo
-
Oleanolic and ursolic acids were used as lead compounds to synthesize a series of pentacyclic triterpenoid derivatives bearing ethylenediamine, butanediamine, or hexanediamine groups at the C-3 position. The potential antiproliferative activity of these compounds was examined in A549 (human non-small cell lung cancer cells), MCF-7 (human breast cancer cells), and HeLa (human cervical carcinoma cells) cells. Methyl 3β-O-[4-(2-aminoethylamino)-4-oxo-butyryl]olean-12-ene-28-oate (DABO-Me) was identified as a promising antiproliferative agent in vitro and in vivo. DABO-Me strongly suppressed the proliferation of A549, MCF-7, and HeLa cells (IC50=4–7μM). In MCF-7 cells, DABO-Me upregulated the pro-apoptotic protein Bax, downregulated the anti-apoptotic protein Bcl-2, promoted the release of cytochrome c, and activated caspase-3/9. Transwell and flow cytometry assays showed that DABO-Me inhibited MCF-7 cell proliferation, migration, and invasion, and induced apoptosis and S phase arrest. In vitro and in vivo experiments indicated that DABO-Me inhibited MCF-7 cell proliferation and suppressed tumor growth. Taken together, these results indicate that DABO-Me could be developed as an effective antitumor drug.
- Feng, Bin,Li, Jiaqi,Tian, Tian,Yu, Jiawen,Zhang, Xiyue,Zhang, Yang,Zhao, Chunhui,Zhao, Longxuan
-
p. 962 - 970
(2020/11/03)
-
- 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.
-
-
- 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
-
-
- 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
-
-
- Ursolic and oleanolic acid derivatives with cholinesterase inhibiting potential
-
Triterpenoids are in the focus of scientific interest, and they were evaluated for many pharmacological applications among them their ability to act as inhibitors of cholinesterases. These inhibitors are still of interest as drugs that improve the life quality of patients suffering from age-related dementia illnesses especially of Alzheimer's disease. Herein, we prepared several derivatives of ursolic and oleanolic acid and screened them in Ellman's assays for their ability to inhibit acetylcholinesterase and/or butyrylcholinesterase, and for each of the active compounds the type of inhibition was determined. As a result, several compounds were shown as good inhibitors for acetylcholinesterase and butyrylcholinesterase even in a micromolar range. An ursolic acid derived hydroxyl-propinyl derivative 10 was a competitive inhibitor for butyrylcholinesterase with an inhibition constant of Ki = 4.29 μM, and therefore being twice as active as gold standard galantamine hydrobromide. The best inhibitor for acetylcholinesterase, however, was 2-methyl-3-oxo-methyl-ursoloate (18), acting as a mixed-type inhibitor showing Ki = 1.72 μM and Ki′ = 1.28 μM, respectively.
- Loesche, Anne,K?witsch, Alexander,Lucas, Susana D.,Al-Halabi, Zayan,Sippl, Wolfgang,Al-Harrasi, Ahmed,Csuk, René
-
-
- Semi-synthesis and Structure–Activity Relationship of Neuritogenic Oleanene Derivatives
-
(3S,4R)-23,28-Dihydroxyolean-12-en-3-yl (2E)-3-(3,4-dihydroxyphenyl)acrylate (1 a), which possesses significant neuritogenic activity, was isolated from the traditional Chinese medicine (TCM) plant, Desmodium sambuense. To confirm the structure and to assess biological activity, we semi-synthesized 1 a from commercially available oleanolic acid. A series of novel 1 a derivatives was then designed and synthesized for a structure–activity relationship (SAR) study. All synthetic derivatives were characterized by analysis of spectral data, and their neuritogenic activities were evaluated in assays with PC12 cells. The SAR results indicate that the number and position of the hydroxy groups on the phenyl ring and the triterpene moiety, as well as the length of the (saturated or unsaturated) alkyl chain that links the phenyl ring with the triterpene critically influence neuritogenic activity. Among all the tested compounds, 1 e [(3S,4R)-23,28-dihydroxyolean-12-en-3-yl (2E)-3-(3,4,5-trihydroxyphenyl)acrylate] was found to be the most potent, inducing significant neurite outgrowth at 1 μm.
- Bian, Linglin,Cao, Shining,Cheng, Lihong,Nakazaki, Atsuo,Nishikawa, Toshio,Qi, Jianhua
-
supporting information
p. 1972 - 1977
(2018/09/06)
-
- 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
-
p. 16782 - 16794
(2018/10/23)
-
- 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)
-
- Sensitized Aliphatic Fluorination Directed by Terpenoidal Enones: A "visible Light" Approach
-
In our continued effort to address the challenges of selective sp3 C-H fluorination on complex molecules, we report a sensitized aliphatic fluorination directed by terpenoidal enones using catalytic benzil and visible light (white LEDs). This sensitized approach is mild, simple to set up, and an economical alternative to our previous protocol based on direct excitation using UV light in a specialized apparatus. Additionally, the amenability of this protocol to photochemical flow conditions and preliminary evidence for electron-transfer processes are highlighted.
- Bume, Desta Doro,Harry, Stefan Andrew,Pitts, Cody Ross,Lectka, Thomas
-
p. 1565 - 1575
(2018/02/09)
-
- 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.
- -
-
Page/Page column 51
(2018/03/28)
-
- Oleanolic acid derivatives as well as preparation method and application thereof
-
The invention provides oleanolic acid derivatives as well as a preparation method and application thereof. The derivatives have a structure represented by a formula (5) in the description. A novel green pesticide with high efficiency, low toxicity, low residues, high selectivity and friendliness to environments is developed through the study of the derivatives.
- -
-
Paragraph 0052; 0053; 0054
(2018/04/21)
-
- 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.
- -
-
Page/Page column 86; 87
(2018/03/28)
-
- Synthesis and anti-influenza virus evaluation of triterpene-sialic acid conjugates
-
We are interested in new non-natural glycosides with sialic acid conjugates and their biological activities. We report the synthesis of eleven non-natural occurring glycosides, which are triterpene (glycyrrhetinic acid and its derivatives)-sialic acid conjugates, and their inhibitory activities against influenza virus sialidases and influenza virus multiplication in MDCK host cells. Deoxoglycyrrhetol-sialic acid conjugates (6d and 6e) and oleanolic acid-sialic acid conjugates (7d and 7e) showed strong inhibitory activities against three subtypes of influenza virus sialidases. These four compounds (6d, 6e, 7d and 7e) showed clear inhibition to influenza virus multiplication but not to MDCK host cell survival.
- Tsuji, Mitsuru,Sriwilaijaroen, Nongluk,Inoue, Hideo,Miki, Kazuhiko,Kinoshita, Kaoru,Koyama, Kiyotaka,Furuhata, Kimio,Suzuki, Yasuo,Takahashi, Kunio
-
-
- Triterpenoid Hydroxamates as HIF Prolyl Hydrolase Inhibitors
-
Pentacyclic triterpenoid acids (PCTTAs) are pleiotropic agents that target many macromolecular end-points with low to moderate affinity. To explore the biological space associated with PCTTAs, we have investigated the carboxylate-to-hydroxamate transformation, discovering that it de-emphasizes affinity for the transcription factors targeted by the natural compounds (NF-κB, STAT3, Nrf2, TGR5) and selectively induces inhibitory activity on HIF prolyl hydrolases (PHDs). Activity was reversible, isoform-selective, dependent on the hydroxamate location, and negligible when this group was replaced by other chelating elements or O-alkylated. The hydroxamate of betulinic acid (5b) was selected for further studies, and evaluation of its effect on HIF-1α expression under normal and hypoxic conditions qualified it as a promising lead structure for the discovery of new candidates in the realm of neuroprotection.
- Minassi, Alberto,Rogati, Federica,Cruz, Cristina,Prados, M. Eugenia,Galera, Nuria,Jinénez, Carla,Appendino, Giovanni,Bellido, M. Luz,Calzado, Marco A,Caprioglio, Diego,Mu?oz, Eduardo
-
p. 2235 - 2243
(2018/10/20)
-
- Synthesis of oleanolic acid analogues and their cytotoxic effects on 3T3 cell line
-
Background: Oleanolic acid (OA) is a known natural compound with many important biological activities. Thirteen oleanolic acid derivatives linked at C-3 and C-28 were synthesized and their structures were confirmed by1H-and13C NMR and mass spectral analyses. Among them, compounds 4, 6, 8-10, 12, 13 were synthesized for the first time. They were evaluated for their cytotoxic activity. They showed proliferative effect at low concentrations while cytotoxic effect was observed at high concentrations in a dose dependent manner. Methods: We have first synthesized compounds 1 and 2 from the reaction of methyl iodide and OA. Compound 1 was reduced with LiAlH4 to give compound 3, and compound 2 gave compound 9 with MOMBr as a new compound. The compound 10 was then obtained from the reduction of compound 9 with LiAlH4 as a new oleanolic acid derivative. A diol derivative 11 was synthesized from OA and LiAlH4 at the room temperature. Compound 4 was obtained from the reaction of compound 3 with CBr4 as a new analogue of OA, and the reduction of compound 4 afforded compound 5 as a known product. In addition, we synthesized compounds 6-8 from compound 3 using MsCl, MeI and p-nitrobenzoyl chloride, respectively, in good yields. Compounds 6 and 8 are new analogues of OA. The new compounds 12 and 13 were also synthesized starting from OA using with MOMBr and TBDMSiCl as the reagents. The all synthesized compounds were purified by using column chromatography and/or crystallization. Results: In the present study, thirteen OA derivatives linked at C-28 and (or) C-3 were synthesized and evaluated for their cytotoxic activity on 3T3 cell lines which are the standard fibroblast cell lines, derived from Swiss albino mouse embryo tissue. 3T3 cell viability was observed at low concentrations of the tested triterpenoids while they displayed anti-proliferative effect at higher concentrations. Conclusion: Oleanolic acid 28-methyl ester (2) showed fairly different behavior from all the other compounds tested and found to be the least cytotoxic compound. However, at 200 μM concentration, it exhibited the same cytotoxicity with compounds 3, 9 and 10 around 58-59%. Among the tested 13 compounds, 7 exhibited the most drastic decline for the viability from 12,5 μM to 25 μM concentration. Compound 6 displayed the most cytotoxic effect, almost in all concentrations, particularly at 6.25 and 25 μM concentrations while the highest cytotoxic effect at 50 μM was observed for compound 11 among all the tested triterpenoids. As a result, all the tested OA derivatives showed proliferative effect at 1,56 μM although no proliferative effect was observed for OA. Moreover, OA exhibited higher cytotoxic effect than its derivatives, particularly at higher concentrations (50, 100, 200 μM) with an exception for compound 11. Because, the latter showed highest proliferative effect at lowest concentration, and highest anti-proliferative effect at highest concentration which surpassed all the OA derivatives.
- Tuncay, Salih,Senol, Halil,Guler, Eray Metin,Ocal, Nuket,Secen, Hasan,Kocyigit, Abdurrahim,Topcu, Gulacti
-
p. 617 - 625
(2018/08/17)
-
- Improvement of synthesis method of 2-cyano-3,12-dioxo oleanane-1,9 (11)-diene-28-carboxylic acid
-
The invention discloses a synthesis technology of 2-cyano-3,12-dioxo oleanane-1,9 (11)-diene-28-carboxylic acid (CDDO), and relates to the technical field of medicines and chemical engineering. The CDDO compounds (CDDOs) are semisynthetic tritererpenoids with the highest known anticancer and anti-inflammatory activity at present and are compounds with broad development and application prospects. The synthesis method of the CDDO reported in the literature at present has the defects of being long in path, fussy in post-treatment, unfriendly to environment and high in cost. The method is a simplified six-step synthesis path, the post-treatment and purification processes are simple, the cost is relatively low, the yield is greatly improved and an important basis is provided for industrial production and subsequent scientific research. The formula is as shown in the specification.
- -
-
Paragraph 0034; 0035; 0036; 0037; 0038; 0039
(2017/08/28)
-
- 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
-
p. 2276 - 2283
(2017/09/01)
-
- 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).
- -
-
Page/Page column 81; 82; 88; 89
(2017/04/11)
-
- Multiple Enone-Directed Reactivity Modes Lead to the Selective Photochemical Fluorination of Polycyclic Terpenoid Derivatives
-
In the realm of aliphatic fluorination, the problem of reactivity has been very successfully addressed in recent years. In contrast, the associated problem of selectivity, that is, directing fluorination to specific sites in complex molecules, remains a great, fundamental challenge. In this report, we show that the enone functional group, upon photoexcitation, provides a solution. Based solely on orientation of the oxygen atom, site-selective photochemical fluorination is achieved on steroids and bioactive polycycles with up to 65 different sp3 C-H bonds. We have also found that γ-, β-, homoallylic, and allylic fluorination are all possible and predictable through the theoretical modes reported herein. Lastly, we present a preliminary mechanistic hypothesis characterized by intramolecular hydrogen atom transfer, radical fluorination, and ultimate restoration of the enone. In all, these results provide a leap forward in the design of selective fluorination of complex substrates that should be relevant to drug discovery, where fluorine plays a prominent role.
- Pitts, Cody Ross,Bume, Desta Doro,Harry, Stefan Andrew,Siegler, Maxime A.,Lectka, Thomas
-
supporting information
p. 2208 - 2211
(2017/02/23)
-
- 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 of ring-C modified oleanolic acid derivatives and their cytotoxic evaluation
-
Ring-C of oleanolic acid was chemically modified by treating with NBS under a variety of experimental conditions. The structures of the synthesized compounds were established by spectral analysis (1H &13C NMR and Mass). All the compounds were evaluated against a panel of five human cancer cell lines by using MTT assay. Among the tested compounds, 2 and 7 showed significant activity against breast cancer cell line, MCF-7. Most significantly, compound 7 showed several folds enhanced activity against MCF-7 cancer cell lines (IC50: 2.96?μM) than that of the parent (1) and the intermediate compound (6). Flow cytometric analysis revealed that these compounds arrested the cell cycle in G0/G1 phase and induced mitochondrial mediated apoptosis.
- Pattnaik, Banita,Lakshma Nayak, Vadithe,Ramakrishna, Sistla,Venkata Mallavadhani, Uppuluri
-
p. 152 - 158
(2016/08/15)
-
- Saponin of which monosaccharide units are D-mannose, as well as preparation method and application of saponin in pharmacy
-
The invention belongs to the technical field of medicines, provides saponin of which monosaccharide units are D-mannose, as well as a preparation method and application of the saponin in pharmacy, and particularly relates to oleanolic acid saponin and betulinic acid saponin, of which the monosaccharide units are the D-mannose, a preparation method of the oleanolic acid saponin and the betulinic acid saponin, and the application of the oleanolic acid saponin and the betulinic acid saponin in preparation of anti-influenza medicines. According to the saponin disclosed by the invention, natural products including oleanolic acid and betulinic acid are used as raw materials, firstly ester groups are introduced at a C-28 position through structural modification, and then D-mannose in alpha-configuration is introduced at a C-3 position so that the saponin of which the monosaccharide units are the D-mannose and which can restrain highly pathogenic influenza virus H5N1 from infecting host cells is obtained. According to the saponin disclosed by the invention, pharmacological experiments are performed, results indicate that saponin compounds have an obvious effect of restraining the process that the highly pathogenic influenza virus H5N1 invades the host cells, and can be further used for preparing medicines for preventing or treating influenza viruses, and preparing medicines in united use with other antivirus medicines and medical compositions comprising the saponin.
- -
-
Paragraph 0025; 0026; 0027
(2016/11/17)
-
- 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
-
-
- Protonated montmorillonite-mediated highly specific isomerization of oleanolic acid esters: Application to the synthesis of Δ13(18)-CDDO-Me
-
A one-pot highly specific isomerization of oleanolic acid esters (5a-g) to δ-oleanolic acid esters (6a-g) was achieved in the presence of proton-exchanged montmorillonite (H-mont) under mild reaction conditions. This protocol could proceed smoothly on a 15.0 gram scale. Based on this methodology, the synthesis of the biologically active compound Δ13(18)-CDDO-Me (4) was realized.
- Chen, Dongyin,Zhang, Pu,Sun, Yan,Wang, Pengfei,Zhang, Can,Kong, Lingyi,Zhang, Ji,Sun, Hongbin,Wen, Xiaoan
-
p. 11154 - 11161
(2016/12/09)
-
- 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.
-
p. 433 - 442
(2016/04/05)
-
- Design, synthesis, and biofunctional evaluation of novel pentacyclic triterpenes bearing O-[4-(1-piperazinyl)-4-oxo-butyryl moiety as antiproliferative agents
-
A series of pentacyclic triterpenoids derivatives bearing O-[4-(1-piperazinyl)-4-oxo-butyryl moiety has been synthesized and investigated for their potential antiproliferative activities. Pentacyclic triterpenoids derivative compounds were synthesized by a four or six step synthetic procedure. The activity studies were evaluated using Cell Counting Kit-8 method, and Western blotting analysis on A549 cells, MCF-7 cells and Hela cells. Compounds methyl 3-O-[4-(1-piperazinyl)-4-oxo-butyryl]olean-12-ene-28-oate (OA-4) and compound 2-O-[4-(1-piperazinyl)-4-oxo-butyryl]-3,23-dihydroxyurs-12-ene-28-oate (AA-5) were found to be promising antiproliferative agents. These compounds show potentiality for further optimization as antitumor drugs.
- Zhao, Chun-Hui,Zhang, Cui-Li,Shi, Jin-Jie,Hou, Xi-Yan,Feng, Bin,Zhao, Long-Xuan
-
supporting information
p. 4500 - 4504
(2015/10/12)
-
- 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 0045
(2014/05/06)
-
- Inhibition of human enterovirus 71 replication by pentacyclic triterpenes and their novel synthetic derivatives
-
A large number of bioactive pentacyclic triterpenoids have been shown to have multiple biological activities. This study was conducted to evaluate the inhibitory activities of 6 newly synthesized and novel pentacyclic triterpenoids against enterovirus 71 (EV71). The parent compound, ursolic acid (UA), showed the greatest inhibitory activity against EV71, while oleanolic acid (OA), asiatic acid (AA), and synthetic derivatives of 18-β-glycyrrhetinic acid (GA) and OA also exhibited inhibitory effects, although to lesser extents. The results suggest these compounds show potential for further optimization as antiviral candidates for treatment of EV71 infections.
- Zhao, Chun-Hui,Xu, Jie,Zhang, Ying-Qiu,Zhao, Long-Xuan,Feng, Bin
-
p. 764 - 771
(2016/10/06)
-
- 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)
-
- 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)
-
- Sulfamates of methyl triterpenoates are effective and competitive inhibitors of carbonic anhydrase II
-
Carbonic anhydrase II, belonging to one of the most important enzyme groups of the human body, is a well-studied isozyme from the family of the carbonic anhydrases. Since it is involved in several physiological processes, it has been a pharmaceutical target for many years. In this study we synthesized a number of sulfamates derived from pentacyclic methyl triterpenoates, and we demonstrate their potential as carbonic anhydrase II inhibitors using the well-established photometric 4-nitrophenyl acetate assay. Inhibition constants, as an indicator of their inhibition strength, were in the micromolar range; one compound (10, methyl (3β) 3-(aminosulfonyloxy)-oleanoate) showed a Ki value as low as 0.3 μM. This Ki value is comparable to that of acetazolamide which is a potent carbonic anhydrase inhibitor and a drug for the treatment of glaucoma.
- Schwarz, Stefan,Sommerwerk, Sven,Lucas, Susana D.,Heller, Lucie,Csuk, René
-
-
- Synthesis and anti-cancer activity of some novel C-17 analogs of ursolic and oleanolic acids
-
A series of seventeen novel analogs of ursolic and oleanolic acid were synthesized (60-98 %), and evaluated for their anti-cancer potential against a panel of eight human cancer cell lines. Compounds (3-10) showed comparable or better activities than their respective parent compounds against SiHa and HeLa (Cervix), A-549 (Lung), and IMR-32 (Neuroblastoma) cancer cell lines. Significantly, among the bromoalkyl esters (11-19), compound 13 showed promising anti-cancer activity against Leukemia THP-1 cell line at 10 μM concentration. In this series, it is interesting to note that the increase in chain length has an adverse effect on the activity.
- Mallavadhani, Uppuluri V.,Mahapatra, Anita,Pattnaik, Banita,Vanga, Nagireddy,Suri, Nitasha,Saxena, Ajit K.
-
p. 1263 - 1269
(2013/04/10)
-
- METHOD FOR SYNTHESIZING 2-CYANO-3,12-DIOXOOLEAN-1, 9(11)-DIEN-28-OIC ACID METHYL ESTER AND DERIVATIVES THEREOF
-
The present invention is a method for preparing triterpenoids such as 2-cyano-3,12-dioxoolean-1,9-dien-28-methyl ester and derivatives thereof from oleanic acid, ursolic acid, betulinic acid, sumaresinolic acid or hederagenin.
- -
-
Paragraph 0106
(2013/11/19)
-
- Triterpenoids and Compositions Containing the Same
-
The present invention provides triterpenoids produced from natural compounds such as oleanolic acid, ursolic acid, betulinic acid, and hederagenin.
- -
-
Paragraph 0103
(2013/11/19)
-
- 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
-
p. 1726 - 1738
(2013/03/29)
-
- 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
-
p. 115 - 121
(2013/10/22)
-
- 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
-
p. 549 - 555
(2013/01/13)
-
- Inhibitors of bacterial biofilms and related methods
-
Certain multi-cyclic compounds 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.
- -
-
Page/Page column 66
(2012/12/13)
-
