989-72-0Relevant academic research and scientific papers
A TRITERPENE ACID CONSTITUENT OF SALVIA LANATA
Mukherjee, K. S.,Bhattacharya, M. K.,Ghosh, P. K.
, p. 2416 - 2417 (1982)
The petrol extract of the whole plant (aerial parts and roots) of Salvia lanata yielded a new triterpene acid, 3-epi-ursolic acid.Key Word Index-Salvia lanata; Labiatae; 3-epi-ursolic acid
Cytotoxicity of oleanolic and ursolic acid derivatives toward hepatocellular carcinoma and evaluation of NF-κB involvement
Fontana, Gianfranco,Bruno, Maurizio,Notarbartolo, Monica,Labbozzetta, Manuela,Poma, Paola,Spinella, Alberto,Rosselli, Sergio
, (2019/06/19)
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.
Design, synthesis, and screening of novel ursolic acid derivatives as potential anti-cancer agents that target the HIF-1α pathway
Wu, Jie,Zhang, Zhi-Hong,Zhang, Lin-Hao,Jin, Xue-Jun,Ma, Juan,Piao, Hu-Ri
supporting information, p. 853 - 858 (2019/02/07)
The transcription factor hypoxia-inducible factor-1α (HIF-1α) plays an important role in tumor angiogenesis, growth, and metastasis and is recognized as an important potential therapeutic target for cancer. Here, we designed and synthesized three novel series of ursolic acid derivatives containing an aminoguanidine moiety and evaluated them as HIF-1α inhibitors and anti-cancer agents using human cancer cell lines. Most of the compounds exhibited significant inhibition of HIF-1α transcriptional activity, as measured using a Hep3B cell-based luciferase reporter assay. Among these compounds, 7b was the most potent inhibitor of HIF-1α expression under hypoxic conditions (IC50 4.0 μM) and did not display significant cytotoxicity against any cell lines tested. The mechanism of action of 7b was investigated, we found that 7b downregulated HIF-1α protein expression, possibly by suppressing its synthesis, reduced production of vascular endothelial growth factor, and inhibited the proliferation of cancer cells.
Synthesis and biological evaluation of ursolic acid derivatives containing an aminoguanidine moiety
Wu, Jie,Ma, Song,Zhang, Tian-Yi,Wei, Zhi-Yu,Wang, Hui-Min,Guo, Fang-Yan,Zheng, Chang-Ji,Piao, Hu-Ri
, p. 959 - 973 (2019/05/04)
Three series of ursolic acid derivatives containing an aminoguanidine moiety were designed, synthesized, and evaluated for anti-bacterial and anti-inflammatory activity. Some compounds displayed potent anti-bacterial activity against Gram-positive bacterial strains (including multidrug-resistant clinical isolates) and Gram-negative bacterial strains, with minimum inhibitory concentration (MIC) values in the range of 2–64 μg/mL. Compounds 3a, 5a, and 7l showed significant inhibitory activity against the Gram-positive bacterial strain Staphylococcus aureus RN 4220, the Gram-negative bacterial strain Escherichia coli 1924, and four multidrug-resistant Gram-positive bacterial strains, with MIC values of 2 and 4 μg/mL. In anti-inflammatory tests, most of the compounds exhibited potent activity, in particular compound 3a displayed the most potent activity with 81.61% inhibition after intraperitoneal administration, which was more potent than ursolic acid and the reference drugs (ibuprofen and indomethacin). The cytotoxic activity of compound 3a was assessed in HeLa, Hep3B, and A549 cells.
Ursolic and oleanolic acid derivatives with cholinesterase inhibiting potential
Loesche, Anne,K?witsch, Alexander,Lucas, Susana D.,Al-Halabi, Zayan,Sippl, Wolfgang,Al-Harrasi, Ahmed,Csuk, René
, p. 23 - 32 (2019/01/04)
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.
Synthesis of novel [3,2-b] furan-fused pentacyclic triterpenoids via gold - Catalyzed intramolecular heterocyclization of 2-alkynyl-3-oxotriterpene acids
Gubaidullin, Rinat R.,Khalitova, Rezeda R.,Galimshina, Zulfiya R.,Spivak, Anna Yu
, p. 1888 - 1899 (2018/03/13)
A direct and atom-economical synthetic route to new [3,2-b] furan-fused pentacyclic triterpenoids has been developed, using gold-catalyzed 5-exo-dig heterocyclization of accessible 2-alkynyl derivatives of betulonic, ursonic, and oleanonic acids.
Semisynthesis, cytotoxicity, antimalarial evaluation and structure-activity relationship of two series of triterpene derivatives
Cargnin, Simone Tasca,Staudt, Andressa Finkler,Medeiros, Patrícia,de Medeiros Sol Sol, Daniel,de Azevedo dos Santos, Ana Paula,Zanchi, Fernando Berton,Gosmann, Grace,Puyet, Antonio,Garcia Teles, Carolina Bioni,Gnoatto, Simone Baggio
supporting information, p. 265 - 272 (2018/02/15)
In this report, we describe the semisynthesis of two series of ursolic and betulinic acid derivatives through designed by modifications at the C-3 and C-28 positions and demonstrate their antimalarial activity against chloroquine-resistant P. falciparum (W2 strain). Structural modifications at C-3 were more advantageous to antimalarial activity than simultaneous modifications at C-3 and C-28 positions. The ester derivative, 3β-butanoyl betulinic acid (7b), was the most active compound (IC50 = 3.4 μM) and it did not exhibit cytotoxicity against VERO nor HepG2 cells (CC50 > 400 μM), showing selectivity towards parasites (selectivity index > 117.47). In combination with artemisinin, compound 7b showed an additive effect (CI = 1.14). While docking analysis showed a possible interaction of 7b with the Plasmodium protease PfSUB1, with an optimum binding affinity of ?7.02 kcal/mol, the rather low inhibition displayed on a Bacillus licheniformis subtilisin A protease activity assay (IC50 = 93 μM) and the observed accumulation of ring forms together with a delay of appearance of trophozoites in vitro suggests that the main target of 3β-butanoyl betulinic acid on Plasmodium may be related to other molecules and processes pertaining to the ring stage. Therefore, compound 7b is the most promising compound for further studies on antimalarial chemotherapy. The results obtained in this study provide suitable information about scaffolds to develop novel antimalarials from natural sources.
Effective synthesis of novel furan-fused pentacyclic triterpenoids via anionic 5-exo dig cyclization of 2-alkynyl-3-oxotriterpene acids
Gubaidullin, Rinat R.,Yarmukhametova, Darina S.,Nedopekina, Darya A.,Khalitova, Rezeda R.,Spivak, Anna Yu.
, p. 100 - 116 (2017/08/10)
An efficient synthetic route to biologically interesting furan-fused pentacyclic triterpenoids with a furan moiety 2,3-annelated to the terpenoid skeleton has been developed. New heterocyclic triterpenoids have been obtained in moderate to good yields by base-promoted 5-exo-dig cyclization of the pent-4-yn-1-one moiety in ring А of the 2-alkynyl-3-oxotriterpene acids of lupane, ursane and oleane type.
Effective synthesis of novel C(2)-propargyl derivatives of betulinic and ursolic acids and their conjugation with β-d-glucopyranoside azides via click chemistry
Spivak, Anna Yu.,Gubaidullin, Rinat R.,Galimshina, Zulfiya R.,Nedopekina, Darya A.,Odinokov, Victor N.
, p. 1249 - 1256 (2016/02/16)
A new synthetic approach to the incorporation of an alkynyl group into pentacyclic triterpenoids was developed and utilized to prepare C(2)-propargyl derivatives of lupane- and ursane-type triterpenoic acids. Novel triterpenoid derivatives with a propynyl group at the C(2) atom were successfully used for click chemistry bioconjugation with glucopyranoside azides.
Synthesis and antitumor activity evaluation of novel ursolic acid derivatives
Meng, Yan-Qiu,Zhang, Liang-Feng,Liu, Dong-Ying,Liu, Li-Wei,Zhang, Yi,Zhao, Min-Jie
, p. 280 - 288 (2016/04/05)
Eleven novel ursolic acid (UA) derivatives were designed and synthesized with modification at positions of C-2, C-3, and C-28 of UA. Their structures were confirmed by MS, 1H NMR, and elemental analysis. Their in vitro cytotoxicities against various cancer cell lines (HeLa, HepG2, and BGC-823) were evaluated by MTT assay. The results indicated that all compounds could inhibit cell proliferation of HeLa, HepG2, and BGC-823 cells. Among them, compounds I3 and I4 showed more potent cytotoxicity on these three tumor cells than gefitinib (positive control), worthy to be studied further.
