17990-42-0Relevant articles and documents
Synthesis and biological evaluation of T-OA analogues as the cytotoxic agents
Xu, Kuo,Xu, Xin,Chu, Fuhao,Wang, Mina,Wang, Penglong,Li, Guoliang,Song, Jixiang,Zhang, Yuzhong,Lei, Haimin
, p. 6257 - 6269 (2015)
Abstract The lead compound T-OA, 3β-hydroxyolean-12-en-28-oic acid-(3,5,6-trimethylpyrazine-2-yl) methyl ester, which exhibited promising anticancer effects in vitro and in vivo, has previously been reported. According to the structural features, a series of novel T-OA analogues were synthesized via amino condensation reaction. These analogues' cytotoxic activities were evaluated on five cancer cell lines (Bel-7402, HepG-2, HT-29, Hela, BGC-823) and hepatic stellate cell line (HSC-6). Among the candidates, compounds 8 and 16 showed promising effects; 3β-hydroxy-lup-20(29)-ene-28-oic acid-(3,5,6-trimethylpyrazin-2-yl) methyl amine (16) even possessed superior bioactivities to positive drugs (cisplatin and ursolic acid), which was worthy of further study. In addition, structure-activity relationships and Clog P values of T-OA analogues were briefly discussed.
Novel A-ring cleaved analogs of oleanolic and ursolic acids which affect growth regulation in NRP.152 prostate cells
Finlay, Heather J.,Honda, Tadashi,Gribble, Gordon W.,Danielpour, David,Benoit, Nicole E.,Suh, Nanjoo,Williams, Charlotte,Sporn, Michael B.
, p. 1769 - 1772 (1997)
Syntheses of eight novel A-ring cleaved oleanane and ursane analogs are described. These compounds were assessed for their ability to inhibit cell proliferation in NRP. 152 prostate cells. Four A-ring cleaved derivatives showed significant activity; 5β-(1-methyl-2-ethyl)-10α-(3-aminopropyl)- des-A-urs-12-en-28-oic acid was the most active compound, (IC50, 0.3 μM).
Synthesis and in vitro activity of oleanolic acid derivatives against Chlamydia trachomatis and Staphylococcus aureus
Kazakova, Oxana,Rubanik, Liudmila,Smirnova, Irina,Poleschuk, Nikolay,Petrova, Anastasia,Kapustsina, Yuliya,Baikova, Irina,Tret’yakova, Elena,Khusnutdinova, Elmira
, p. 1408 - 1418 (2021)
A series of nitrogen-containing modificants with amide, arylidene or heterocyclic fragments of oleanolic, oleanonic and 2,3-indolo-oleanolic acids have been synthesized and evaluated for activity against C. trachomatis and key ESKAPE pathogens. Oleanolic acid conjugates with homopyperazine 3, N-hydroxymethyl-homopyperazine 4, and diethylenetriamine 23 demonstrated a high inhibitory activity against C. trachomatis with chemotherapeutic index (CTI) 8 and >8, while 3-amino-3,4-seco-4(23)-en-erythrodiol 22 was found to be a leader compound with significant activity (MIC 3.125 μg/mL). Compounds 3 and 22 showed a moderate activity against MRSA with MICs of 8 and 4 μg/mL. Compounds 2, 3, and 23 exhibited remarkable activities against NCI-60 subpanel (GI50 ranges from 0.18 to 2.21 μM) exceeding the activity of sorafenib with compound 23 as a leader (GI50 0.17 μM for melanoma LOX IMVI). [Figure not available: see fulltext.]
Pentacyclic triterpene derivatives possessing polyhydroxyl ring A inhibit Gram-positive bacteria growth by regulating metabolism and virulence genes expression
Huang, Lirong,Luo, Heng,Li, Qiji,Wang, Daoping,Zhang, Jianxin,Hao, Xiaojiang,Yang, Xiaosheng
, p. 64 - 75 (2015)
The hydroxyl group in ring A of pentacyclic triterpene is essential for antibacterial activity. Pentacyclic triterpenes bearing three hydroxyl groups in ring A were mainly found in plants and displayed significant antibacterial activity. However, no study
Ring-A cleavage of 3-oxo-olean-12-en-28-oic acid by the fungus Chaetomium longirostre
Shirane, Noboru,Hashimoto, Yutaka,Ueda, Kazuo,Takenaka, Hideyuki,Katoh, Kenji
, p. 99 - 104 (1996)
3-Oxo-olean-12-en-28-oic acid was transformed by the filamentous fungus Chaetomium longirostre into 3,4-seco-olean-12-en-4-ol-3,28-dioic acid and the 21β-hydroxylated compound. A cell-free preparation derived from the fungus converted 3-oxo-olean 12-en-28-oic acid into 3,4-seco-olean-12-en-4-ol-3,28- dioic acid. The ring-A cleavage activity was detected in the soluble fraction of the cell-free preparation and showed a requirement for NADPH.
Triterpenoids as novel natural inhibitors of human cathepsin L
Ramalho, Suelem D.,De Sousa, Lorena R. F.,Nebo, Liliane,Maganhi, Stella H.,Caracelli, Ignez,Zukerman-Schpector, Julio,Lima, Maria Inês S.,Alves, Marcio F. M.,Da Silva, M. Fátima Das G. F.,Fernandes, Jo?o B.,Vieira, Paulo C.
, p. 1354 - 1363 (2014)
Cathepsins L (catL) and B play an important role in tumor progression and have been considered promising therapeutic targets in the development of novel anticancer agents. Using a bioactivity-guided fractionation, a series of triterpenoids was identified as a new class of competitive inhibitors towards cathepsin L with affinity values in micromolar range. Among the 14 compounds evaluated, the most promising were 3-epiursolic acid (3), 3-(hydroxyimino)oleanolic acid (9), and 3-(hydroxyimino)masticadienoic acid (13) with IC50 values of 6.5, 2.4, and 2.6 μM on catL, respectively. Most of the evaluated triterpenoids do not inhibit cathepsin B. Thus, the evaluated compounds exhibit a great potential to help in the design of new inhibitors with enhanced potency and affinity towards catL. Docking studies were performed in order to gain insight on the binding mode and SAR of these compounds.
Strong inhibitory activity and action modes of synthetic maslinic acid derivative on highly pathogenic coronaviruses: Covid-19 drug candidate
Al-Karmalawy, Ahmed A.,Alasiri, Ahlam,Ali, Mohamed A.,Choua?b, Karim,Chrouda, Amani,Dhahri, Abdelwaheb,Gharbi, Jawhar,Jannet, Hichem Ben,Kutkat, Omnia,Mostafa, Ahmed,Pashameah, Rami Adel,Shehata, Mahmoud,Soltane, Raya
, (2021)
In late December 2019, a novel coronavirus, namely severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), escaped the animal–human interface and emerged as an ongoing global pandemic with severe flu-like illness, commonly known as coronavirus disea
A Series of Oleanolic Acid Derivatives as Anti-Hepatitis B Virus Agents: Design, Synthesis, and in Vitro and in Vivo Biological Evaluation
Yan, Wenqiang,Zhang, Chenze,Li, Bi,Xu, Xin,Liang, Miao,Gu, Shun,Chu, Fuhao,Xu, Bing,Ren, Jian,Wang, Penglong,Lei, Haimin
, (2016)
A series of oleanolic acid derivatives were synthesized by diverse reactions, including the introduction of conjugated alkadiene and epoxy ring moieties formed by means of photosensitized oxidation. Eosin Y was used as photosensitizer during this process. Next the cytotoxicity of the products was evaluated on HepG2.2.15 cells to determine the appropriate treatment concentration for the subsequent experiments. Most of the OA derivatives exhibited anti-HBV antigens secretion activity in HepG2.2.15 cells. Among the tested compounds, OA-4 (3.13 μg/mL) showed significant activity against the secretion of HBsAg, HBeAg, and HBV DNA replication with inhibitory ratios of 90.52% ± 1.78%, 31.55% ± 3.65%, and 94.57% ± 3.11% after 6 days, respectively. Besides, OA-4 was further investigated in a duck model with DHBV infection. When OA-4 was administered at a dosage of 500 mg/kg, the results revealed a significant inhibitory effects of DHBV at 19.94% ± 2.87%, 28.80% ± 3.62% and 29.25% ± 2.65% at days 5, 10, and 3 after the cessation of OA-4 treatment, respectively. It's worth noting that OA-4 is superior to lamivudine in the inhibition of rebound of viral replication rate. The structure-activity relationships of OA derivatives had been preliminary discussed, which should be useful to explore further novel anti-HBV agents.
Synthesis of new betulonic and oleanonic acid amides
Giniyatullina,Kazakova,Salimova,Tolstikov
, p. 68 - 72 (2011)
Amides of betulonic and oleanonic acids with diethylenetriamine, triethylenetetramine, and spermidine were synthesized. Antitumor activity in vitro was not found for the conjugate of betulonic acid with diethylenetriamine.
Prelog
, (1932)
An efficient semi-synthesis of 1-hydroxyl oleanolic acid analogs
Zhang, Da-Hui,Fang, Wei-Shuo,Wang, Shao-Rong
, p. 595 - 601 (2017)
An efficient route for the semi-synthesis of either 1α- or 1β-OH epimers of 1-hydroxy-3-deoxyolean-12-en-28-oic acid (1), 6–8 steps from oleanolic acid is reported. The synthesis involves stereoselective formation of α,β-unsaturated epoxy ketone and subsequent Wharton reaction as key steps, offering a new access to the 1-O-substituted oleanolic acid-type pentacyclic triterpenoids.
Fluorescent probes for subcellular localization during osteclast formation
Wu, Jing,Shen, Qi,Wang, Yue,Zhao, Dan,Peng, Chen,Li, Jian-Xin
, p. 911 - 914 (2014)
Labeling of a small bioactive molecule with fluorescent probe has been becoming an essential tool in cell biology to reveal the subcellular distribution and the location of a molecular target. QOA-8a is a novel molecule with potent antiosteoporotic effect in vivo. To investigate the molecular mechanism of QOA-8a, novel fluorescence-tagged chemical probes as bioactive as their parent molecule were designed and synthesized. The fluorescent compound 12 showed a more potent inhibitory activity on RANKL-induced osteoclastogenesis at 2 μM compared with that of QOA-8a. Microscopy experiments revealed that almost all of probe 12 accumulated in the fusing region, with little in the osteoclast precursors or the mature osteoclasts during osteoclast formation. The result suggests the location of the binding target of QOA-8a, which might greatly narrow down the search field of the target protein(s).
Antibacterial and antitumoral properties of 1,2,3-triazolo fused triterpenes and their mechanism of inhibiting the proliferation of HL-60 cells
Daelemans, Dirk,De Jonghe, Steven,Dehaen, Wim,Hu, Haibo,Krasniqi, Besir,Li, Yang,Luyten, Walter,Persoons, Leentje,Wang, Rui
, (2021)
Antimicrobial resistance and cancer are two important problems affecting human health. Actively developing novel antibiotics and anticancer medicines is a priority. Natural pentacyclic triterpenoids have attracted wide attention due to their significant biological activities. In this study, a series of 1,2,3-triazolo fused triterpenoids (betulin, oleanolic acid and ursolic acid) were functionalized on the A-ring by an in-house developed multi-component triazolization reaction. The compounds were investigated for antitumoral activity in twelve cancer cell lines and were also tested for antibacterial activity against four bacteria. In terms of anticancer effects, compounds 5b-f and 8a-d displayed strong cytotoxic activity in pancreatic adenocarcinoma (Capan-1), chronic myeloid leukemia (Hap-1), acute myeloid leukemia (HL-60), acute lymphoblastic leukemia (Jurkat) and non-Hodgkin lymphoma (Rec-1) cell lines. Among them, compound 5f exhibited the most potent antiproliferative effect on HL-60 cells. Further pharmacological research confirmed that compound 5f caused mitochondrial dysfunction and arrested the cell cycle in the G0/G1 phase to induce apoptosis of HL-60 cells. In addition, compound 5f also induced autophagy to inhibit the proliferation of HL-60 cells. Antibacterial screening revealed that compounds 2a-g and 5a-d showed modest activity against Gram-negative bacteria (Escherichia coli and Salmonella enterica subsp. enterica) with especially compounds 2c and 2d being potent inhibitors of Salmonella enterica subsp. enterica growth. Because of their promising anticancer and antibacterial activity, this series of compounds deserve further study.
Discovery of triterpenoids as potent dual inhibitors of pancreatic lipase and human carboxylesterase 1
He, Rong-Jing,Huo, Hong,Li, Yan-Ran,Pan, Qiu-Sha,Qian, Xing-Kai,Sun, Cheng-Gong,Sun, Lei,Wang, Le-Tian,Wang, Ya-Jie,Yang, Ling,Zhang, Jing,Zhou, Xiang-Lu,Zou, Li-Wei
, p. 629 - 640 (2022/02/09)
Pancreatic lipase (PL) is a well-known key target for the prevention and treatment of obesity. Human carboxylesterase 1A (hCES1A) has become an important target for the treatment of hyperlipidaemia. Thus, the discovery of potent dual-target inhibitors based on PL and hCES1A hold great potential for the development of remedies for treating related metabolic diseases. In this study, a series of natural triterpenoids were collected and the inhibitory effects of these triterpenoids on PL and hCES1A were determined using fluorescence-based biochemical assays. It was found that oleanolic acid (OA) and ursolic acid (UA) have the excellent inhibitory effects against PL and hCES1A, and highly selectivity over hCES2A. Subsequently, a number of compounds based on the OA and UA skeletons were synthesised and evaluated. Structure–activity relationship (SAR) analysis of these compounds revealed that the acetyl group at the C-3 site of UA (compound 41) was very essential for both PL and hCES1A inhibition, with IC50 of 0.75 μM and 0.014 μM, respectively. In addition, compound 39 with 2-enol and 3-ketal moiety of OA also has strong inhibitory effects against both PL and hCES1A, with IC50 of 2.13 μM and 0.055 μM, respectively. Furthermore, compound 39 and 41 exhibited good selectivity over other human serine hydrolases including hCES2A, butyrylcholinesterase (BChE) and dipeptidyl peptidase IV (DPP-IV). Inhibitory kinetics and molecular docking studies demonstrated that both compounds 39 and 41 were effective mixed inhibitors of PL, while competitive inhibitors of hCES1A. Further investigations demonstrated that both compounds 39 and 41 could inhibit adipocyte adipogenesis induced by mouse preadipocytes. Collectively, we found two triterpenoid derivatives with strong inhibitory ability on both PL and hCES1A, which can be served as promising lead compounds for the development of more potent dual-target inhibitors targeting on PL and hCES1A.
Design, synthesis, molecular modelling, and biological evaluation of oleanolic acid-arylidene derivatives as potential anti-inflammatory agents
Mir, Reyaz Hassan,Godavari, Goutami,Siddiqui, Nasir Ali,Ahmad, Bilal,Mothana, Ramzi A.,Ullah, Riaz,Almarfadi, Omer M.,Jachak, Sanjay M.,Masoodi, Mubashir Hussain
, p. 385 - 397 (2021/05/06)
Introduction: Oleanolic acid, a pentacyclic triterpenic acid, is widely distributed in medicinal plants and is the most commonly studied triterpene for various biological activities, including anti-allergic, anti-cancer, and anti-inflammatory. Methods: The present study was carried out to synthesize arylidene derivatives of oleanolic acid at the C-2 position by Claisen Schmidt condensation to develop more effective anti-inflammatory agents. The derivatives were screened for anti-inflammatory activity by scrutinizing NO production inhibition in RAW 264.7 cells induced by LPS and their cytotoxicity. The potential candidates were further screened for inhibition of LPS-induced interleukin (IL-6) and tumour necrosis factor-alpha (TNF-α) production in RAW 264.7 cells. Results: The results of in vitro studies revealed that derivatives 3d, 3e, 3L, and 3o are comparable to that of the oleanolic acid on the inhibition of TNF-α and IL-6 release. However, derivative 3L was identified as the most potent inhibitor of IL-6 (77.2%) and TNF-α (75.4%) when compared to parent compound, and compounds 3a (77.18%), 3d (71.5%), and 3e (68.8%) showed potent inhibition of NO than oleanolic acid (65.22%) at 10μM. Besides, from docking score and Cyscore analysis analogs (3e, 3L, 3n) showed greater affinity towards TNF-α and IL-1β than dexamethasone. Conclusion: Herein, we report a series of 15 new arylidene derivatives of oleanolic acid by Claisen Schmidt condensation reaction. All the compounds synthesized were screened for their anti-inflammatory activity against NO, TNF-α and IL-6. From the data, it was evident that most of the compounds exhibited better anti-inflammatory activity.
