4481-62-3Relevant articles and documents
A convergent synthesis of novel alkyne–azide cycloaddition congeners of betulinic acid as potent cytotoxic agent
Dangroo, Nisar A.,Singh, Jasvinder,Rath, Santosh K.,Gupta, Nidhi,Qayum, Arem,Singh, Shashank,Sangwan, Payare L.
, p. 1 - 12 (2017)
In an endeavour to develop potent anti-tumor agents from betulinic acid (BA), a series of C-28 derived 1,2,3-triazolyl derivatives were designed and synthesized by employing Cu(I) catalyzed Huisgen 1,3-dipolar cycloaddition reaction. All the derivatives were evaluated for cytotoxic activity by MTT assay against five different human cancer cell lines: lung (A549), colon (HCT116), prostate (PC3), pancreatic (MIA PaCa-2) and breast (T47D). The data revealed that compounds 11c, 11d, 11g, 11h and 13a possess most promising cytotoxic potential. The compound 11h was one of the most active compounds, with IC50 values in the range of 4–6?μM against all the five cancer cell lines. The results of this study suggested that derivatives with free –OH (11c, 11d and 11g) and free –COOH (11h and 13a) substitutions in the triazole moiety introduced at the C-28 position significantly improved the anti-tumor activity and may be the favourable position to synthesize potent anticancer leads from BA. Introduction of a non polar alkyl groups at C-28 position (10, 12 and 14) resulted in the significant loss of the activity. Further, DAPI staining, ROS generation and wound healing experiments revealed that compound 11h induces apoptosis in HCT-116 cells.
Synthesis of novel lupane triterpenoid-indazolone hybrids with oxime ester linkage
Khlebnicova, Tatyana S.,Shishkina, Svetlana V.,Zicāne, Daina,Piven, Yuri A.,Tetere, Zenta,Baranovsky, Alexander V.,Rāvi?a, Irisa,Lakhvich, Fedor A.,Kumpi??, Viktors,Rijkure, Inese,Mieri?a, Inese,Peipi??, Uldis,Turks, Māris
, p. 77 - 89 (2017)
An efficient protocol for the synthesis of novel lupane triterpenoid-indazolone hybrids with oxime ester linkage has been developed from naturally accessible precursor betulin. For the first time a series of betulonic acid-indazolone hybrids have been synthesized via an acylation of corresponding 6,7-dihydro-1H-indazol-4(5H)-one oximes with betulonic acid chloride. Diastereoselective reduction of the obtained betulonic acid conjugates with NaBH4resulted in a formation of betulinic acid-indazolone hybrids in excellent yields. The configuration of the key compounds has been fully established by X-ray and 2D NMR analysis.
Novel Betulinic Acid-Nucleoside Hybrids with Potent Anti-HIV Activity
Wang, Qiang,Li, Yujiang,Zheng, Liyun,Huang, Xiaowan,Wang, Yanli,Chen, Chin-Ho,Cheng, Yung-Yi,Morris-Natschke, Susan L.,Lee, Kuo-Hsiung
, p. 2290 - 2293 (2020)
Novel betulinic/betulonic acid-nucleoside hybrids were synthesized as possible new anti-HIV agents. Among the synthesized hybrids, two compounds were highly effective against HIV. Compared with AZT and DSB, compounds 10a (IC50= 0.0078 μM, CC50= 9.6 μM) and 10b (IC50= 0.020 μM, CC50= 23.8 μM) showed more potent or equipotent, respectively, anti-HIV activity but displayed lower cytotoxicity.
Synthesis and anti-HCV entry activity studies of β-cyclodextrin- pentacyclic triterpene conjugates
Xiao, Sulong,Wang, Qi,Si, Longlong,Shi, Yongying,Wang, Han,Yu, Fei,Zhang, Yongmin,Li, Yingbo,Zheng, Yongxiang,Zhang, Chuanling,Wang, Chunguang,Zhang, Lihe,Zhou, Demin
, p. 1060 - 1070 (2014)
In our previous studies, oleanolic acid (OA) and echinocystic acid (EA), isolated from Dipsacus asperoides, were found to have anti-HCV entry properties. The major issue for members of this type of triterpene is their low water solubility. In this study, a series of new water-soluble triazole-bridged β-cyclodextrin (CD)-pentacyclic triterpene conjugates were synthesized via click chemistry. Thanks to the attached β-CD moiety, all synthesized conjugates showed lower hydrophobicity (Alog P) than their parent compounds. Several conjugates exhibited moderate anti-HCV entry activity. With the exception of per-O-methylated β-CD-pentacyclic triterpene conjugates, all other conjugates showed no cytotoxicity based on an alamarBlue assay carried out with HeLa, HepG2, MDCK, and 293T cells. More interestingly, the hemolytic activity of these conjugates disappeared upon the introduction of β-CDs. Easy access to such conjugates that combine the properties of β-CD and pentacyclic triterpenes may provide a way to obtain a new class of anti-HCV entry inhibitors. An awesome CD collection: A series of water-soluble triazole-bridged β-cyclodextrin (CD)-pentacyclic triterpene conjugates were synthesized, and their hydrophobicity, anti-HCV entry activities, and toxicity were studied. Easy access to such conjugates may provide a way to obtain a new class of anti-HCV entry inhibitors.
Lupane triterpenes and derivatives with antiviral activity
Baltina,Flekhter,Nigmatullina,Boreko,Pavlova,Nikolaeva,Savinova,Tolstikov
, p. 3549 - 3552 (2003)
Betulin and betulinic acid have been modified at the C-3 and C-28 positions and the antiviral activity of derivatives has been evaluated in vitro. It was found that simple modifications of the parent structure of lupane triterpenes produced highly effective agents against influenza A and herpes simplex type 1 viruses.
Betulonic acid—cyclodextrins inclusion complexes
Sbarcea, Laura,Lede?i, Adriana,Udrescu, Lucre?ia,V?ru?, Renata-Maria,Barvinschi, Paul,Vlase, Gabriela,Lede?i, Ionu?
, p. 2787 - 2797 (2019)
Betulonic acid (BA) is a pentacyclic lupane-type triterpenoid possessing valuable pharmacological activities, exhibiting very low water solubility. Inclusion complexes between the substance and cyclodextrins (CDs) were obtained in order to improve its solubility and consequently its bioavailability. The aim of this study was to investigate the guest–host interaction of BA with γ-cyclodextrin (γ-CD) and its derivative, 2-hydroxypropyl-γ-cyclodextrin (HP-γ-CD), in solution and in solid state in order to prove the formation of inclusion complexes between the components. The kneading method was used for the inclusion complexes preparation, and different analytical techniques such as thermal analysis, powder X-ray diffractometry, universal attenuated total reflectance Fourier transform IR spectroscopy (UATR-FTIR) and UV spectroscopy were employed to investigate the interaction between substances. The stoichiometry of the inclusion complex BA/HP-γ-CD was found to be 1:1 by employing continuous variation method, and the apparent stability constant was calculated as 1855.55?M?1 using Benesi–Hildebrand equation. Structural studies of the inclusion complexes were carried out using molecular modeling techniques in order to explain the complexation mechanism. The results of this study confirm the formation of inclusion complexes between BA and cyclodextrins both in solution and in solid state.
Modified Method for Measuring the Solubility of Pharmaceutical Compounds in Organic Solvents by Visual Camera
Tang, Ning,Shi, Wei,Yan, Weidong
, p. 35 - 40 (2016)
A modified synthetic method with a high definition visual camera technique for measuring the solubility of solutes in solvents or mixed solvents was proposed. To verify the reliability of the experimental apparatus, the solubility of NH4Cl in water was determined at different temperatures. The relative standard errors were less than 1%, compared to the literature data. The solubilities of betulonic acid in six organic solvents from (278.15 to 313.15) K were measured and correlated with the Apelblat equation and universal quasichemical equation, respectively. The modified method was quite concise and user-friendly, and made the process of dissolution to become visualized and automatic.
3-Epihydroxy lup-20(29)-en-19(28)-olide: partial synthesis, antitopoisomerase activity, and 3D molecular docking
Mandal, Amitava,Ghosh, Ashim,Ghosh, Shilpi,Shil, Suranjan,Bothra, Asim Kumar,Ghosh, Pranab
, p. 1087 - 1095 (2016)
A novel method for the partial synthesis of the rare triterpenoid, 3-epihydroxy lup-20(29)-en-19(28)-olide, and 1 from betulinic acid is reported. The binding efficiency, mode of binding for different compounds to the central catalytic domain of topoisomerase IIα, was calculated from a complete 3D molecular docking study on the crystal structure of the enzyme (1bgw, pdb). The compounds 1, 2b, and 2d showed a dose-dependent inhibition of catalytic activity of topoisomerase IIα.
Method for Preparing Betulonic Acid from Betula pendula Birch Bark
Levdanskii,Levdanskii,Kuznetsov
, p. 766 - 768 (2016)
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Microbial transformations of two lupane-type triterpenes and anti-tumor-promoting effects of the transformation products
Akihisa, Toshihiro,Nishino, Hoyoku,Takamine, Yoshio,Yoshizumi, Kazuo,Tokuda, Harukuni,Kimura, Yumiko,Ukiya, Motohiko,Nakahara, Toro,Yokochi, Toshihiro,Ichiishi, Eiichiro
, p. 278 - 282 (2002)
Microbial transformation of betulin (1), a lupane-type triterpene obtained from the bark extract of white birch (Betula platyphylla Sukatshev var. japonica), and its chemical oxidation product, betulonic acid (2), by the fungus Chaetomium longirostre yielded 4,28-dihydroxy-3,4-seco-lup-20(29)-en-3-oic acid (3) and 4-hydroxy-3,4-seco-lup-20(29)-ene-3,28-dioic acid (4) from 1, and 4,7β,17-trihydroxy-3,4-seco-28-norlup-20(29)-en-3-oic acid (5) and 7β,15α-dihydoxy-3-oxolup-20(29)-en-28-oic acid (6) from 2. The four metabolites, 3-6, along with 1 and 2, were evaluated for their inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells as a primary screening test for inhibitors of tumor promotion. All of the triterpenes tested showed potent inhibitory effects, with the four metabolites 3-6 exhibiting the more potent effects.
Betulinic acid derivative and application thereof
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Paragraph 0042-0044; 0049, (2021/06/22)
The invention belongs to the field of medicines, and particularly relates to betulinic acid derivatives and application thereof. The invention mainly provides a compound as shown in the following formula I, a stereoisomer, nitrogen oxide, pharmaceutically acceptable salt or prodrug of the compound and application of the compound to preparation of drugs, and the drugs are used for preventing or treating liver diseases or protecting the liver.
The Effect of Experimental BCG Antigen–Betulin-Derived Conjugates on the Guinea Pig Immunological Response
Koshkin, I. N.,Kulakov, I. V.,Vlasenko, V. S.
, p. 837 - 844 (2021/08/25)
Abstract: The immunopotentiating properties of BCG vaccine strain antigen conjugated with betulin derivatives have been evaluated. The experiments were carried out on agouti guinea pigs (n = 20). The animals of the experimental groups (n = 5) were immunized with the following antituberculosis drugs: group 1, with antigens of the BCG vaccine strain conjugated with betulinic acid; group 2, with BCG antigens conjugated with betulonic acid; and group 3, with the BCG vaccine. The animals of the control group (n = 5) were injected with a saline solution. All the animals were infected with a virulent culture of Mycobacterium bovis (strain 8) on day 30 after the administration of antituberculosis drugs. The blood sampling for the assessment of the immune status was conducted on day 30 after the administration of drugs and day 30 after the infection with M. bovis. The designed conjugates were found to display immunopotentiating activity characterized by a 1.7–3.8-fold increase in the number of immunocompetent cells and an increase in the neutrophil functional activity observed to a greater degree in the guinea pig group 2. After infection with M. bovis some key parameters of the immune system, such as a T-lymphocyte count and the activity of enzymatic (myeloperoxidase) and nonenzymatic (cationic proteins) bactericidal systems of neutrophilic granulocytes significantly increased in groups 2 and 3, which implied the highest antituberculosis activity of the agents administered to these animals. The guinea pigs were euthanized 45 days after the infection with M. bovis. The next pathoanatomical experiments proved that the vaccine strain conjugates with betulonic acid and the BCG vaccine induced marked resistance against the pathogenic mycobacteria. The protection indexes for these agents were approximately the same and achieved 66 and 71%, respectively.
Enhancement of the antioxidant and skin permeation properties of betulin and its derivatives
Duchnik, Wiktoria,Günther, Andrzej,Klimowicz, Adam,Kucharski, ?ukasz,Makuch, Edyta,Nowak, Anna,Pe?ech, Robert
, (2021/06/21)
This study investigated the antioxidant activity DPPH, ABTS, and Folin–Ciocalteu methods of betulin (compound 1) and its derivatives (compounds 2–11). Skin permeability and accumulation associated with compounds 1 and 8 were also examined. Identification of the obtained products (compound 2–11) and betulin isolated from plant material was based on the analysis of1H-NMR and13C-NMR spectra. The partition coefficient was calculated to determine the lipophilicity of all compounds. In the next stage, the penetration through pig skin and its accumulation in the skin were evaluated of ethanol vehicles containing compound 8 (at a concentration of 0.226 mmol/dm3), which was characterized by the highest antioxidant activity. For comparison, penetration studies of betulin itself were also carried out. Poor solubility and the bioavailability of pure compounds are major constraints in combination therapy. However, we observed that the ethanol vehicle was an enhancer of skin permeation for both the initial betulin and compound 8. The betulin 8 derivative showed increased permeability through biological membranes compared to the parent betulin. The paper presents the transformation of polycyclic compounds to produce novel derivatives with marked antioxidant activities and as valuable intermediates for the pharmaceutical industry. Moreover, the compounds contained in the vehicles, due to their mechanism of action, can have a beneficial effect on the balance between oxidants and antioxidants in the body, minimizing the effects of oxidative stress. The results of this work may contribute to knowledge regarding vehicles with antioxidant potential. The use of vehicles for this type of research is therefore justified.
