105452-47-9

Upstream product

• 884310-54-7 acetic acid-(3β-acetoxy-ursen-(12)-oic acid-(28))-anhydride 
• 64-17-5 ethanol 
• 77-52-1 Ursolic acid 
• 108-24-7 acetic anhydride 
• 77-52-1 ursolic acid 
• 77-52-1 ursolic acid 
• 64-19-7 acetic acid 
• 75-36-5 acetyl chloride 
• 160911-62-6 3β-(acetyloxy)-11α,12α-epoxy-14α-hydroxyurs-28-oic acid δ-lactone 
• 86996-88-5 3β-acetoxyurs-12-en-28-al 

Downstream Products

• 545-46-0 uvaol 
• 71623-71-7 11-oxo-ursolic acid acetate 
• 35959-08-1 3β-acetoxyurs-11-en-28,13-olide 
• 160911-71-7 3β-(acetyloxy)-12α-bromo-13-hydroxyursan-28-oic acid γ-lactone 
• 1437303-18-8 3β-phthaloyl-urs-12-en-28-carboxamide 
• 920283-62-1 C₄₂H₆₁NO₅ 

Relevant academic research and scientific papers

Selective killing of cancer cells with triterpenoic acid amides - The substantial role of an aromatic moiety alignment

2,3-Di-O-acetyl-triterpenoic acid derived amides possessing a (2β, 3β) configuration in ring A and two acetyl groups were previously shown to possess high cytotoxicity for human tumor cell lines but to exhibit low cytotoxicity for non-malignant mouse fibroblasts. In this study, augustic acid (1) and 2-epi-corosolic acid (2) were chosen as starting points for the synthesis of analogs. While augustic acid derived 3-quinolinyl amide 9 gave low EC50values in SRB assays but was cytotoxic for all lines, the isomeric 4-isoquinolinyl amide 21 was very cytotoxic for the tumor cell lines but significantly less cytotoxic for the mouse fibroblasts NIH 3T3. In addition, a triacetylated 4-isoquinolinyl derivative of asiatic acid (28) gave EC50?=?80?nM (for A2780 ovarian cancer cells). As shown by additional experiments (acridine orange/propidium iodide staining, fluorescence spectroscopy and cell cycle investigations) these compounds act mainly by apoptosis.

Ursolic acid derivatives induce cell cycle arrest and apoptosis in NTUB1 cells associated with reactive oxygen species

Twenty-three ursolic acid (1) derivatives 2-24 including nine new 1 derivatives 5, 7-11, 20-22 were synthesized and evaluated for cytotoxicities against NTUB1 cells (human bladder cancer cell line). Compounds 5 and 17 with an isopropyl ester moiety at C-17-COOH and a succinyl moiety at C-3-OH showed potent inhibitory effect on growth of NTUB1 cells. Compounds 23 and 24 with seco-structures prepared from 1 also showed the increase of the cytotoxicity against NTUB1 cells. Exposure of NTUB1 to 5 (40 μM) and 23 (20 and 50 μM) for 24 h significantly increased the production of reactive oxygen species (ROS) while exposure of NTUB1 to 5 (20 and 40 μM) and 23 (20 and 50 μM) for 48 h also significantly increased the production of ROS while exposure of cells to 17 did not increase the amount of ROS. Flow cytometric analysis exhibited that treatment of NTUB1 with 5 or 17 or 23 led to the cell cycle arrest accompanied by an increase in apoptotic cell death after 24 or 48 h. These data suggest that the presentation of G1 phase arrest and apoptosis in 5- and 23-treated NTUB1 for 24 h mediated through increased amount of ROS in cells exposed with 5 and 23, respectively, while the presence of G2/M arrest before accumulation of cells in sub-G1 phase in 5-treated cells for 48 h also due to increased amount of ROS in cells exposed with 5. The inhibition of tubulin polymerization and cell cycle arrest at G2/M following by apoptosis presented in the cell cycle of 23 also mediates through the increase amount of ROS induced by treating NTUB1 with 23 for 48 h.

The cytotoxic activity of ursolic acid derivatives

Ursolic acid and 2α-hydroxyursolic acid isolated from apple peels were found to show growth inhibitory activity against four tumor cell lines, HL-60, BGC, Bel-7402 and Hela. Structural modifications were performed on the C-3, C-28 and C-11 positions of ursolic acid and the cytotoxicity of the derivatives was evaluated. The SAR revealed that the triterpenes possessing two hydrogen-bond forming groups (an H-donor and a carbonyl group) at positions 3 and 28 exhibit cytotoxic activity. The configuration at C-3 was found to be important for the activity. Introduction of an amino group increased the cytotoxicity greatly. A 3β-amino derivative was 20 times more potent than the parent ursolic acid. The 28-aminoalkyl dimer compounds showed selective cytotoxicity.

Spermine amides of selected triterpenoid acids: Dynamic supramolecular system formation influences the cytotoxicity of the drugs

Cancer is a global disease of great importance, and the need for novel cytotoxic drugs is still eminent. A series of spermine amides of several selected triterpene acids (betulonic, heterobetulonic, oleanolic, ursolic and platanic acid) have been synthesized to search for new cytotoxic and antimicrobial agents. The compounds have also been subjected to the investigation of their physico-chemical characteristics (ability to self-assemble), and to an in silico comparative calculation of their physico-chemical and ADME parameters. In the in vitro screening tests with several target compounds (8a-8c and 11c), their cytotoxicity changed with prolonged time, which appeared to be a result of formation of dynamic supramolecular networks. This phenomenon is important in investigation of the effect of self-assembly on biological activity. The most important compounds in this series were spermine derivatives of heterobetulonic acid (3b) and ursolic acid (8b), showing cytotoxicity 5 μM and 10 μM, respectively, on all tested cancer cell lines. Comparable cytotoxicity was also displayed by 13b, formerly a model compound prepared for testing of the synthetic procedures, the 1,2-diaminoethane derivative. The target compounds 3b and 8b displayed antimicrobial activity on Staphylococcus aureus, Streptococcus mutans and Listeria monocytogenes at a concentration 6.25 μM. Supramolecular characteristics of several compounds were documented by the TEM and SEM micrographs showing fibrous, partially helical, networks, and UV measurements showing changes in the intensity of UV signals, also indicating formation of supramolecular systems.

Novel pH-sensitive polysialic acid based polymeric micelles for triggered intracellular release of hydrophobic drug

Polysialic acid (PSA), a non-immunogenic and biodegradable natural polymer, is prone to hydrolysis under endo-lysosomal pH conditions. Here, we synthesized an intracellular pH-sensitive polysialic acid-ursolic acid conjugate by a condensation reaction. To further test the drug loading capability, we prepared paclitaxel-loaded polysialic acid-based amphiphilic copolymer micelle (PTX-loaded-PSAU) by a nanoprecipitation method. Results showed PTX-loaded-PSAU exhibited well-defined spherical shape and homogeneous distribution. The drug-loading was 4.5% with an entrapment efficiency of 67.5%. PTX released from PTX-loaded-PSAU was 15% and 42% in 72 h under simulated physiological condition (pH 7.4) and mild acidic conditions (pH 5.0), respectively. In addition, In vitro cytotoxicity assay showed that PTX-loaded-PSAU retained anti-tumor (SGC-7901) activity with a cell viability of 53.8% following 72 h incubation, indicating PTX-loaded-PSAU could efficiently release PTX into the tumor cells. These results indicated that the pH-responsive biodegradable PTX-loaded-PSAU possess superior extracellular stability and intracellular drug release ability.

Discovery of ursolic acid prodrug (NX-201): Pharmacokinetics and in vivo antitumor effects in PANC-1 pancreatic cancer

The aim of our study was to develop ursolic acid (UA) prodrugs in order to overcome UA's weakness, which has an extremely low bioavailability. UA-medoxomil (NX-201), one of our UA prodrugs, showed an improved bioavailability about 200 times better than UA in rodent model. According to in vivo test performed with PANC-1 xenograft SCID mouse model, tumor growth rate decreased dose-dependently and 100 mg/kg dose of NX-201 had an anticancer effect comparable to gemcitabine. Most of all the combination of NX-201 (50 mg/kg, po, daily) and gemcitabine (40 mg/kg, iv, 2 times per week) even reduced tumor size after three weeks.

Synthesis of [3β-acetoxy-urs-12-en-28-oyl]-1-monoglyceride and investigation on its anti tumor effects against BGC-823

Ursolic acid (UA) as the leader compound was designed to prepare a series of derivatives (three novel compounds UA-1a, UA-1b and UA-2) by modification at the C3 and C28 positions. Their chemical structures were confirmed by IR, 1H NMR and MS. The cytotoxic activity of the derivatives was evaluated against HepG2, BGC-823 and HT-29 by the MTT assay. The novel derivative UA-1a, [3β-acetoxy-urs-12-en-28-oyl]-1-monoglyceride showed significant anti-growth ability against the assayed cancer cell lines, particularly against BGC-823, while low cytotoxicity to human normal gastric cell line GES-1. Further investigation revealed that UA-1a could induce apoptotic events of the treated BGC-823 cells, such as comet-like DNA bend, sub-G0/G1 phase accumulation and phosphatidylserine externalization. The activity of Caspase-3 was found to be up-regulated, while the expression of Bcl-2 and Survivin were down-regulated in UA-1a treated cells. UA-1a might trigger the death of BGC-823 cells by inducing apoptosis via the mitochondria pathway. UA-1a exerted stronger ability than Taxol to retard tumor growth in nude mice without leaving apparent toxicity to the hosts. The experimental data suggested that UA-1a would have a therapeutic potential in the treatment of gastric cancer.

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.

Drug resistance reversal potential of ursolic acid derivatives against nalidixic acid- and multidrug-resistant Escherichia coli

As a part of our drug discovery program, ursolic acid was chemically transformed into six semi-synthetic derivatives, which were evaluated for their antibacterial and drug resistance reversal potential in combination with conventional antibiotic nalidixic acid against the nalidixic acid-sensitive and nalidixic acid-resistant strains of Escherichia coli. Although ursolic acid and its all semi-synthetic derivatives did not show antibacterial activity of their own, but in combination, they significantly reduced the minimum inhibitory concentration of nalidixic acid up to eightfold. The 3-O-acetyl-urs-12-en-28-isopropyl ester (UA-4) and 3-O-acetyl-urs-12-en-28-n-butyl ester (UA-5) derivatives of ursolic acid reduced the minimum inhibitory concentration of nalidixic acid by eightfold against nalidixic acid-resistant and four and eightfold against nalidixic acid-sensitive, respectively. The UA-4 and UA-5 were further evaluated for their synergy potential with another antibiotic tetracycline against the multidrug-resistant clinical isolate of Escherichia coli-KG4. The results showed that both these derivatives in combination with tetracycline reduced the cell viability in concentration-dependent manner by significantly inhibiting efflux pump. This was further supported by the in silico binding affinity of UA-4 and UA-5 with efflux pump proteins. These ursolic acid derivatives may find their potential use as synergistic agents in the treatment of multidrug-resistant Gram-negative infections. Drug resistance reversal potential and mechanism of natural compound ursolic acid and its derivative UA-4 were deduced through inhibition of ATP-dependent efflux pumps. Inhibition of efflux pumps is useful in (i) lowering the dose of antibiotics; (ii) reducing the drug resistance development frequency; and (iii) increasing the efficacy of antibiotics against multidrug-resistant Escherichia coli strains.

Phytochemical investigation of Tabebuia palmeri

Phytochemical investigation of the stems, flowers, and leaves of Tabebuia palmeri has led to the isolation of a novel compound, 6-(1-hydroxyundec-3-enyl)- tetrahydropyran-2-one, and 16 known compounds, viz. 1-hexadecanol, 1-triacontanol, stigmast-5-en-3β-ol, 2-hydroxy-3-(3-methylbut-2-enyl)-1,4- naphthoquinone (lapachol), methyl 3,4-dimethoxybenzoate, 2-acetyl-4H,9H- naphtho[2,3-b]furan-4,9-dione, 3,4-dimethoxybenzoic acid, 4-hydroxybenzoic acid, 3,4-dihydroxybenzoic acid, 3β-hydroxy-12-ursen-28-oic acid, 5,7,4β-trihydroxyflavone, β-sitosteryl-β-D-galactoside, 6-O-(p-hydroxybenzoyl)-epiaucubin, 4-O-β-D-glucosylbenzoic acid, 9Z,12Z-octadecadienoic acid, and hexadecanoic acid. Except lapachol, all these phytoconstituents were isolated from the Tabebuia palmeri for the first time, and their structures were established on the basis of spectral data analysis and chemical reactions.