6246-46-4Relevant articles and documents
Synthesis and antitumor potential of new arylidene ursolic acid derivatives via caspase-8 activation
He, Baoen,Zhu, Zuchang,Chen, Fenglian,Zhang, Rong,Chen, Weiqiang,Zhang, Te,Wang, Tao,Lei, Jiamei
, (2021)
Continuing our studies on NO-donating ursolic acid–benzylidene derivatives as potential antitumor agents, we designed and synthesized a series of new arylidene derivatives containing NO-donating ursolic acid and aromatic heterocyclic units. Compounds 5c and 6c showed a significant broad-spectrum antitumor activity. Compound 5c exhibited nearly three- to nine-fold higher cytotoxicity as compared with the parent drug in A549, MCF-7, HepG-2, HT-29, and HeLa cells, and it was also found to be the most potent apoptosis inducer of MCF-7 cells. More importantly, compound 5c arrested the MCF-7 cell cycle in the G1 phase, which was associated with caspase activation and a decrease of the Bcl-2/Bax ratio. Meanwhile, compound 5c caused changes in morphological features, dissipation of the mitochondrial membrane potential, and accumulation of reactive oxygen species. A docking study revealed that the nitroxyethyl moiety of compound 5c may form hydrogen bonds with caspase-8 amino acid residues (SER256 and HIS255). Together, these data suggest that NO-donating ursolic acid–arylidene derivatives are potent apoptosis inducers in tumor cells.
Synthesis and antitumor activity evaluation of ursolic acid derivatives
Meng, Yan-Qiu,Xu, Chuan-Dong,Yu, Ting-Ting,Li, Wei,Li, Qian-Wen,Li, Xiao-Xiao
, p. 359 - 369 (2020)
Eighteen uronic acid derivatives were designed and synthesized, and the cytotoxicities in vitro of two cancer cell lines (BEL7402 and SGC7901) were evaluated by MTT assay. The results showed that the inhibitory rate of the compounds on both cell lines was
Cytotoxic triterpenes from the aerial roots of Ficus microcarpa
Chiang, Yi-Ming,Chang, Jang-Yang,Kuo, Ching-Chuan,Chang, Chi-Yen,Kuo, Yueh-Hsiung
, p. 495 - 501 (2005)
Six triterpenes, 3β-acetoxy-12,19-dioxo-13(18)-oleanene (1), 3β-acetoxy-19(29)-taraxasten-20α-ol (2), 3β-acetoxy-21α, 22α-epoxytaraxastan-20α-ol (3), 3,22-dioxo-20-taraxastene (4), 3β-acetoxy-11α,12α-epoxy-16-oxo-14-taraxerene (5), 3β-acetoxy-25-methoxylanosta-8,23-diene (6) along with nine known triterpenes, 3β-acetoxy-11α,12α-epoxy-14-taraxerene (7), 3β-acetoxy-25-hydroxylanosta-8,23-diene (8), oleanonic acid (9), acetylbetulinic acid (10), betulonic acid (11), acetylursolic acid (12), ursonic acid (13), ursolic acid (14), and 3-oxofriedelan-28-oic acid (15) were isolated from the aerial roots of Ficus microcarpa, and their structures elucidated by spectroscopic methods. The in vitro cytotoxic efficacy of these triterpenes was investigated using three human cancer cell lines, namely, HONE-1 nasopharyngeal carcinoma, KB oral epidermoid carcinoma, and HT29 colorectal carcinoma cells. Compound 8 and pentacyclic triterpenes 9-15 possessing a carboxylic acid functionality at C-28 showed significant cytotoxic activities against the aforementioned cell lines and gave IC50 values in the range 4.0-9.4 μM.
Fluorescent labeling of ursolic acid with FITC for investigation of its cytotoxic activity using confocal microscopy
Frolova, Tatiana S.,Lipeeva, Alla V.,Baev, Dmitry S.,Baiborodin, Sergey I.,Orishchenko, Кonstantin E.,Kochetov, Alexey V.,Sinitsyna, Olga I.
, p. 876 - 887 (2019)
Fluorescent labeling is a widely-used approach in the study of intracellular processes. This method is becoming increasingly popular for studying small bioactive molecules of natural origin; it allows us to estimate the vital intracellular changes which occur under their influence. We propose a new approach for visualization of the intracellular distribution of triterpene acids, based on fluorescent labeling by fluoresceine isothiocyanate. As a model compound we took the most widely-used and best-studied acid in the ursane series – ursolic acid, as this enabled us to compare the results obtained during our research with the available data, in order to evaluate the validity of the proposed method. Experimental tracing of the dynamics of penetration and distribution of the labeled ursolic acid has shown that when the acid enters the cell, it initially localizes on the inner membranes where the predicted target Akt1/protein kinase B – a protein that inhibits apoptosis – is located.
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)
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.
Preventive effect of ursolic acid derivative on particulate matter 2.5-induced chronic obstructive pulmonary disease involves suppression of lung inflammation
Li, Cuini,Chen, Junxian,Yuan, Weiwei,Zhang, Wei,Chen, Hong,Tan, Hongtao
, p. 632 - 640 (2020)
Respiratory diseases like chronic obstructive pulmonary disease (COPD) are associated with the presence of particulate matter 2.5 (PM2.5) in the air. In the present study, the effect of synthesized ursolic acid derivatives on mice model of PM2.5-induced COPD was investigated in vivo. The mice model of COPD was established by the administration of 25 μL of PM2.5 suspension through intranasal route daily for 1 week. The levels of oxidative stress markers and inflammatory cytokines like tumor necrosis factors-α and interleukin-6 in the mice bronchoalveolar fluids increased markedly on administration with PM2.5. However, treatment with ursolic acid derivative caused a significant suppression in PM2.5-induced increase in oxidative stress markers and inflammatory cytokines in dose-dependent manner. Hematoxylin and eosin staining showed excessive inflammatory cell infiltration in pulmonary tissues in mice with COPD. The inflammatory cell infiltration was inhibited on treatment of the mice with ursolic acid derivative. The ursolic acid derivative treatment increased level of superoxide dismutase in mice with COPD. The lung injury induced by PM2.5 in mice was also prevented on treatment with ursolic acid derivative. Thus, ursolic acid derivative inhibits pulmonary tissues damage in mice through suppression of inflammatory cytokine and oxidative enzymes. Therefore, ursolic acid derivative can be of therapeutic importance for treatment of PM2.5-induced COPD.
Synthesis and biological evaluation of ursolic acid-triazolyl derivatives as potential anti-cancer agents
Rashid, Showkat,Dar, Bilal Ahmad,Majeed, Rabiya,Hamid, Abid,Bhat, Bilal Ahmad
, p. 238 - 245 (2013)
A series of ursolic acid-1-phenyl-1H-[1,2,3]triazol-4-ylmethylester congeners have been designed and synthesized in an attempt to develop potent antitumor agents. A regioselective approach using Huisgen 1,3-dipolar cycloaddition reaction of ursolic acid-alkyne derivative with various aromatic azides was employed to target an array of triazolyl derivatives in an efficient manner. Their structures were confirmed by using 1H NMR, 13C NMR, IR and MS analysis. All the compounds were evaluated for anticancer activity against a panel of four human cancer cell lines including A-549 (lung), MCF-7 (breast), HCT-116 (colon), THP-1 (leukemia) and a normal human epithelial cell line (FR-2) using sulforhodamine-B assay. The pharmacological results showed that most of the compounds displayed high level of antitumor activities against the tested cancer cell lines compared with ursolic acid. Compounds 7b, 7g, 7p and 7r were found to be the most potent compounds in this study.
Synthesis and evaluation of ursolic acid-based 1,2,4-triazolo[1,5-a]pyrimidines derivatives as anti-inflammatory agents
Zhang, Tian-Yi,Li, Chun-Shi,Li, Ping,Bai, Xue-Qian,Guo, Shu-Ying,Jin, Ying,Piao, Sheng-Jun
, p. 27 - 38 (2022)
Here, two series of novel ursolic acid-based 1,2,4-triazolo[1,5-a]pyrimidines derivatives were synthesized and screened for their anti-inflammatory activity by evaluating their inhibition effect of using LPS-induced inflammatory response in RAW 264.7 macrophages in vitro; the effects of different concentrations of the compounds on the secretion of nitric oxide (NO) and inflammatory cytokines including TNF-α and IL-6 were evaluated. Their toxicity was also assessed in vitro. Results showed that the most prominent compound 3 could significantly decrease production of the above inflammatory factors. Docking study was performed for the representative compounds 3, UA, and Celecoxib to explain their interaction with cyclooxygenase-2 (COX-2) receptor active site. In vitro enzyme study implied that compound 3 exerted its anti-inflammatory activity through COX-2 inhibition.
New derivatives of ursolic acid through the biotransformation by Bacillus megaterium CGMCC 1.1741 as inhibitors on nitric oxide production
Zhang, Chao,Xu, Shao-Hua,Ma, Bai-Ling,Wang, Wei-wei,Yu, Bo-Yang,Zhang, Jian
, p. 2575 - 2578 (2017)
Microbial transformation of ursolic acid (1) by Bacillus megaterium CGMCC 1.1741 was investigated and yielded five metabolites identified as 3-oxo-urs-12-en-28-oic acid (2); 1β,11α-dihydroxy-3-oxo-urs-12-en-28-oic acid (3); 1β-hydroxy-3-oxo-urs-12-en-28, 13-lactoe (4); 1β,3β, 11α-trihydroxyurs-12-en-28-oic acid (5) and 1β,11α-dihydroxy-3-oxo-urs-12-en-28-O-β-D-glucopyranoside (6). Metabolites 3, 4, 5 and 6 were new natural products. Their nitric oxide (NO) production inhibitory activity was assessed in lipopolysaccharide (LPS) – stimulated RAW 264.7 cells. Compounds 3 and 4 exhibited significant activities with the IC50 values of 1.243 and 1.711?μM, respectively. A primary structure-activity relationship was also discussed.
Design, synthesis, anticancer activity and mechanism studies of novel 2-amino-4-aryl-pyrimidine derivatives of ursolic acid
Gu, Wen,Li, A-Liang,Liu, Qing-Song,Sun, Yue,Wang, Wen-Yan,Yang, Zi-Hui
, p. 2335 - 2350 (2022/02/16)
A series of novel 2-amino-4-aryl-pyrimidine derivatives of ursolic acid were designed, synthesized, and evaluated for their anticancer activities against four cancer cell lines (MCF-7, HeLa, HepG2, and A549) and a human hepatocyte cell line (LO2) via MTT assay. Among these derivatives, compound 7b exhibited potent cytotoxic activity against MCF-7 and HeLa cells with IC50 values of 0.48 ± 0.11 and 0.74 ± 0.13 μM, respectively, and substantially lower cytotoxicity to LO2 cells. Further cellular mechanism studies in MCF-7 cells elucidated that compound 7b could inhibit cell migration, induce cell cycle arrest at S phase and trigger mitochondrial-related apoptosis by increasing the generation of intracellular ROS and decreasing the mitochondrial membrane potential (MMP), which was associated with upregulation of the protein expression level of Bax and downregulation the level of Bcl-2 and the activation of caspase cascade. Western blot analyses also revealed that compound 7b could simultaneously suppress RAS/Raf/MEK/ERK and PI3K/AKT/mTOR signaling pathways, which could be responsible for the induction of apoptosis. Molecular docking study revealed that MEK1 kinase could be one of the possible targets of the title compounds. These results offered a promising scaffold for the investigation of novel targeted anticancer agents.
Synthesis and biological evaluation of pentacyclic triterpenoid derivatives as potential novel antibacterial agents
Wu, Panpan,Tu, Borong,Liang, Jinfeng,Guo, Shengzhu,Cao, Nana,Chen, Silin,Luo, Zhujun,Li, Jiahao,Zheng, Wende,Tang, Xiaowen,Li, Dongli,Xu, Xuetao,Liu, Wenfeng,Zheng, Xi,Sheng, Zhaojun,Roberts, Adam P.,Zhang, Kun,Hong, Weiqian David
, (2021/02/26)
A series of ursolic acid (UA), oleanolic acid (OA) and 18β-glycyrrhetinic acid (GA) derivatives were synthesized by introducing a range of substituted aromatic side-chains at the C-2 position after the hydroxyl group at C-3 position was oxidized. Their antibacterial activities were evaluated in vitro against a panel of four Staphylococcus spp. The results revealed that the introduction of aromatic side-chains at the C-2 position of GA led to the discovery of potent triterpenoid derivatives for inhibition of both drug sensitive and resistant S. aureus, while the other two series derivatives of UA and OA showed no significant antibacterial activity even at high concentrations. In particular, GA derivative 33 showed good potency against all four Staphylococcus spp. (MIC = 1.25–5 μmol/L) with acceptable pharmacokinetics properties and low cytotoxicity in vitro. Molecular docking was also performed using S. aureus DNA gyrase to rationalize the observed antibacterial activity. This series of GA derivatives has strong potential for the development of a new type of triterpenoid antibacterial agent.
