192211-41-9

Upstream product

• 77-52-1 ursolic acid 
• 100-39-0 benzyl bromide 
• 100-44-7 benzyl chloride 

Relevant academic research and scientific papers

A hydrophilic conjugate approach toward the design and synthesis of ursolic acid derivatives as potential antidiabetic agent

In this study, a series of novel ursolic acid (UA) derivatives were designed and synthesized successfully via conjugation of hydrophilic and polar groups at 3-OH and/or 17-COOH position. Molecular docking studies were carried out with the binding of UA and acabose in the active site of α-glucosidase, in order to prove that the hydrophilic/polar moieties can interact with the hydrophobic group of the catalytic pocket and form hydrogen bonds. The bioactivities of these synthesized compounds against α-glucosidase were determined in vitro. Kinetic studies were performed to determine the mechanism of inhibition by compounds 3, 4, 10 and 11. The results indicated that most of the target compounds have significant inhibitory activity, and the compound 3, 4, 10 and 11 were potent inhibitors of α-glucosidase, with the IC50 values of 0.149 ± 0.007, 0.223 ± 0.023, 0.466 ± 0.016 and 0.298 ± 0.021 μM, respectively. These compounds were more potent than parent compound and acarbose. The kinetic inhibition studies revealed that compound 3 and 4 were mix-type inhibitors while compound 10 and 11 were non-competitive inhibitors. Furthermore, the molecular docking studies for these two kinds of compounds suggested that free carboxylic group at either C-3 or C-28 position could remarkably improve inhibitory activity. It is noteworthy that the exploration of relationship between hydrophilic and polar groups of these structures and the hydrophobic group in catalytic pocket is benefited from our rational design of potent α-glucosidase inhibitor.

Synthesis and evaluation as potential antitumor agents of novel ursolic acid derivatives

Novel ursolic acid derivatives were synthesized, and their structures were confirmed by MS, IR, 1H NMR and 13C NMR spectral analysis. In vitro antitumor activities of these compounds against MGC-803 (gastric cancer cell) and Bcap-37 (breast cancer cell) human cancer cell lines were evaluated by MTT assay. The pharmacological screening results revealed that many derivatives exhibited moderate to high activities against the tested cell lines, and that most demonstrated more potent inhibitory activities than that of ursolic acid. Preliminarily mechanism study of representative compound 3h were carried out by acridine orange/ethidium bromide staining, Hoechst 33258 staining, terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling assay, and flow cytometry which indicated that compound 3h can induce cell apoptosis of MGC-803 cells, and the apoptosis ratio reached 34.59 % after 36 h treatment at 10 μM.

Discovery and radiosensitization research of ursolic acid derivatives as SENP1 inhibitors

SUMOylation and deSUMOylation plays an important role in DNA damage response and the formation of radiotherapy resistance. SENP1 is the main specific isopeptidase to catalyze deSUMOylation modification. Inhibiting SENP1 upregulates cancer cell radiosensitivity and it becomes a promising target for radiosensitization. Herein, based on the structure of ursolic acid (UA), a total of 53 pentacyclic triterpene derivatives were designed and synthesized as SENP1 inhibitors. Ten derivatives exhibited better SENP1 inhibitory activities than UA and the preliminary structure-activity relationship was discussed. Most of the UA derivatives were low-cytotoxic, among which compound 36 showed the best radiosensitizing activity with the SER value of 1.45. It was the first study to develop small molecular SENP1 inhibitors as radiosensitizers.

Ursolic amide derivative containing pyrazole heterocycle, and synthesis and application thereof

The present invention provides the structure general formula of a class of pyrazole heterocycle-containing ursolic amide derivatives, further a synthesis route and synthesis steps of the pyrazole heterocycle-containing ursolic amide derivatives, and uses

Synthesis, biological evaluation and SAR studies of ursolic acid 3β-ester derivatives as novel CETP inhibitors

Cholesteryl ester transfer protein (CETP) is an attractive therapeutic target for the prevention and treatment of cardiovascular diseases by lowering low-density lipoprotein cholesterol levels as well as raising high-density lipoprotein cholesterol levels in human plasma. Herein, a series of ursolic acid 3β-ester derivatives were designed, synthesized and evaluated for the CETP inhibiting activities. Among these compounds, the most active compound is U12 with an IC50 value of 2.4 μM in enzymatic assay. The docking studies showed that the possible hydrogen bond interactions between the carboxyl groups at both ends of the molecule skeleton and several polar residues (such as Ser191, Cys13 and Ser230) in the active site region of CETP could significantly enhance the inhibition activity. This study provides structural insight of the interactions between these pentacyclic triterpenoid 3β-ester derivatives and CETP protein for the further modification and optimization.

Antimicrobial properties of amine- and guanidine-functionalized derivatives of betulinic, ursolic and oleanolic acids: Synthesis and structure/activity evaluation

A series of 34 new amine- and guanidine-functionalized derivatives of betulinic, ursolic, and oleanolic acids were synthesized and tested for their antimicrobial activity against the growth of four bacterial strains (Escherichia coli, Acinetobacter baumannii, Pseudomonas aeruginosa, and Staphylococcus aureus (MRSA)) and two fungal strains (Candida albicans and Cryptococcus neoformans). The obtained compounds were also tested for the cytotoxic effect against HEK293 human embryonic kidney cell line and hemolytic activity against human red blood cells. Most of the prepared amino and guanidinium derivatives of betulinic, ursolic, and oleanolic acids showed a considerably higher bacteriostatic activity against methicillin-resistant S. aureus than the parent compounds. The most active compounds (MICs ≤ 0.25 μg/ml or 0.4–0.5 μM) were superior over the clinically used antibiotic vancomycin in the antibacterial effect (MIC of 1 μg/ml or 0.7 μM). Apart from antibacterial activity, new triterpene acid derivatives exhibited excellent antifungal activity against Cryptococcus neoformans, with MICs values being as low as 0.25 μg/ml (0.4 μM), and were approximately 65 times as active as fluconazole, a known antifungal agent. Four most promising compounds we identified (7, 13, 24, and 33) showed not only high bacteriostatic effect, but also low cytotoxicity against mammalian HEK293 cells and high hemolytic selectivity.

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

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.

An Ursolic Acid Derived Small Molecule Triggers Cancer Cell Death through Hyperstimulation of Macropinocytosis

Macropinocytosis is a transient endocytosis that internalizes extracellular fluid and particles into vacuoles. Recent studies suggest that hyperstimulation of macropinocytosis can induce a novel nonapoptotic cell death, methuosis. In this report, we descr

Ursolic acid derivative containing parazole heterocycle as well as synthesis and application thereof

The invention provides a general structural formula of an ursolic acid derivative containing a parazole heterocycle. The invention further provides a synthetic route of the ursolic acid derivative containing the parazole heterocycle and synthesis steps of