122798-61-2Relevant academic research and scientific papers
Anticancer effect of A-ring or/and C-ring modified oleanolic acid derivatives on KB, MCF-7 and HeLa cell lines
Bednarczyk-Cwynar, Barbara,Zaprutko, Lucjusz,Ruszkowski, Piotr,Hladon, Boguslaw
, p. 2201 - 2205 (2012)
New A-ring or/and C-ring modified methyl oleanolate derivatives were prepared. New simple method of synthesis of 3,12-diketone (3) from methyl oleanonate (2) was worked out. The obtained new compounds were tested for cytotoxic activity on KB, MCF-7 and HeLa cell lines. The derivatives had acetoxy, oxo or hydroxyimino function at the C-3 position and in some cases oxo, hydroxyimino or acyloxyimino group at the C-12 position. Almost all of the compounds showed strong cytotoxic activity, higher than unchanged oleanolic acid. The most active substances turned out to be the derivatives with acyloxyimino function, especially 4 and 8d. The Royal Society of Chemistry 2012.
Design and Synthesis of Irreversible Analogues of Bardoxolone Methyl for the Identification of Pharmacologically Relevant Targets and Interaction Sites
Wong, Michael H. L.,Bryan, Holly K.,Copple, Ian M.,Jenkins, Rosalind E.,Chiu, Pak Him,Bibby, Jaclyn,Berry, Neil G.,Kitteringham, Neil R.,Goldring, Christopher E.,O'Neill, Paul M.,Park, B. Kevin
, p. 2396 - 2409 (2016)
Semisynthetic triterpenoids such as bardoxolone methyl (methyl-2-cyano 3,12-dioxooleano-1,9-dien-28-oate; CDDO-Me) (4) are potent inducers of antioxidant and anti-inflammatory signaling pathways, including those regulated by the transcription factor Nrf2. However, the reversible nature of the interaction between triterpenoids and thiols has hindered attempts to identify pharmacologically relevant targets and characterize the sites of interaction. Here, we report a shortened synthesis and SAR profiling of 4, enabling the design of analogues that react irreversibly with model thiols, as well as the model protein glutathione S-transferase P1, in vitro. We show that one of these analogues, CDDO-epoxide (13), is comparable to 4 in terms of cytotoxicity and potency toward Nrf2 in rat hepatoma cells and stably modifies specific cysteine residues (namely, Cys-257, -273, -288, -434, -489, and -613) within Keap1, the major repressor of Nrf2, both in vitro and in living cells. Supported by molecular modeling, these data demonstrate the value of 13 for identifying site(s) of interaction with pharmacologically relevant targets and informing the continuing development of triterpenoids as novel drug candidates.
Gastroprotective and ulcer-healing activity of oleanolic acid derivatives: In vitro-in vivo relationships
Sanchez, Marianela,Theoduloz, Cristina,Schmeda-Hirschmann, Guillermo,Razmilic, Ivan,Yanez, Tania,Rodriguez, Jaime A.
, p. 1349 - 1356 (2006)
The triterpene oleanolic acid 1 and its semisynthetic derivatives 2-7 were assessed for gastroprotective and ulcer-healing effect using human epithelial gastric cells (AGS) and human lung fibroblasts (MRC-5). The ability of the compounds to protect the AGS cells against the damage induced by sodium taurocholate (NaT), to stimulate the cellular reduced glutathione (GSH) and prostaglandin E2 content, to enhance AGS and MRC-5 cell proliferation and to scavenge superoxide anion in vitro was studied. The cytotoxicity of the compounds was assessed towards MRC-5 and AGS cells. In addition, the gastroprotective activity of the compounds was assessed in vivo using the HCl/EtOH-induced ulcer model in mice. All the assayed compounds displayed a significant reduction of AGS cells damage after incubation with NaT. None of the studied compounds was active as a superoxide anion scavenger nor stimulated the GSH content in AGS cell cultures. Compounds 1, 2, 4 and 6 were able to increase the prostaglandin content in AGS cell cultures. Concerning the proliferation assays, a significant stimulating effect was observed for compounds 3 and 7 on AGS cells and for 1 and 7 on MRC-5 fibroblasts. Regarding cytotoxicity, derivatives 2, 4, 6 and 7 were less toxic than the parent compound oleanolic acid. Our results strongly support the predictive capacity of the in vitro assessment of gastroprotective activity allowing the reduction of experimental animals.
Gastroprotective activity of oleanolic acid derivatives on experimentally induced gastric lesions in rats and mice
Astudillo, Luis,Rodriguez, Jaime A.,Schmeda-Hirschmann, Guillermo
, p. 583 - 588 (2002)
The gastroprotective effect of the triterpene oleanolic acid (OA) was assessed on gastric ulceration in rats. The effect of a single oral dose of OA was evaluated at 50, 100 and 200 mg kg-1 in the following models: pylorus ligature (Shay), and aspirin-and ethanol-induced gastric ulcers. A single oral administration of OA at doses of 50, 100 and 200 mg kg-1 inhibited the appearance of gastric lesions induced by ethanol, aspirin and pylorus ligature. In the pylorus ligature and aspirin models, the effect of OA at the selected concentrations was comparable with that of ranitidine at 50 mg kg-1. In the ethanol-induced gastric lesion model, OA showed a dose-dependent activity, and at 100 and 200 mg kg-1 was as active as omeprazole at 20 mg kg-1. The effect of OA, its acetylated and methoxylated derivatives, oleanonic acid and its methyl ester were assessed on HCl/ethanol-induced ulcers in mice at 200 mg kg-1. OA and its methoxylated (OAM) and acetylated (OAAM, OAA) derivatives proved to be active in this animal model. The semisynthetic derivatives OAM and OAAM had the greatest gastroprotective activity, but their effect was not significantly greater than OA. In an acute toxicity test on mice, intraperitoneal administration of OA showed no toxicity at doses up to 600 mg kg-1.
Structure and spasmolytic activity of eucalyptanoic acid from Eucalyptus camaldulensis var. obtusa and synthesis of its active derivative from oleanolic acid
Begum, Sabira,Sultana, Ishrat,Siddiqui, Bina S.,Shaheen, Farhana,Gilani, Anwar H.
, p. 1939 - 1941 (2002)
A new triterpenoid acid named eucalyptanoic acid (1) has been isolated from the fresh uncrushed leaves of Eucalyptus camaldulensis var. obtusa along with two known constituents, β-sitosterol (2) and betulinic acid (3). The structure of 1 has been established as 3β-hydroxyolean-9(11),12-dien-28-oic acid through spectral studies including 1D and 2D NMR. 1 and its acetyl (1a) and acetylmethyl (1b) derivatives were tested for spasmolytic activity. 1b was found to be the most active spasmolytic, mediated through blockade of calcium influx at 1 mg/mL. In the present study 1b was also prepared starting from oleanolic acid (4). Acetylation of 4 gave 4a, which on methylation afforded 4b. Reaction of 4b with N-bromosuccinimide (NBS) furnished 1b. Hence 4 may be regarded as the biogenetic precursor of 1. Compounds 4 and 4a were found inactive at 1 mg/mL, while 4b was moderately active in showing spasmolytic activity.
Total syntheses of (+)-arisugacins F, G
Chen, Ping,Li, Yu,Tang, Yu,Wu, Hao
, (2020)
(+)-Arisugacin F and G are synthesized from commercially available oleanolic acid in 9 and 10 steps, respectively. This strategy features a AgOTf/Pd(PPh3)4-mediated cis/trans olefin isomerization and a highly convergent formal oxa-[3 + 3] cycloaddition between key α, β-unsaturated aldehyde and pyrone, which lays the foundation for efficient and concise synthesis of other natural products with similar terpenoid scaffolds.
Synthesis and anti-HIV activity of oleanolic acid derivatives
Zhu, Yong-Ming,Shen, Jing-Kang,Wang, Hui-Kang,Cosentino,Lee, Kuo-Hsiung
, p. 3115 - 3118 (2001)
Thirteen oleanolic acid derivatives were prepared and evaluated for anti-HIV activity in H9 lymphocytes. Saturating the C12-C13 double bond and converting the C17-carboxyl group to an aminomethyl group led to compounds 13-15 and 19-20, respectively, which showed improved anti-HIV activity. Compound 15 was the most potent derivative with EC50=0.0039 μg/mL and TI=3570.
Degradation of triterpenic compounds from olive-pressing residues. Synthesis of trans-decalin type chiral synthons
García-Granados, Andrés,López, Pilar E.,Melguizo, Enrique,Parra, Andrés,Simeó, Yolanda
, p. 6673 - 6677 (2003)
Three seco-C-ring triterpenic compounds were obtained from oleanolic or maslinic acids from olive-mill solid wastes by photochemical and chemical reactions. From these oleantriene compounds, different remarkable sesquiterpene and nor-sesquiterpene fragments such as 3β-hydroxydrimenol (13) and epoxydecalone (16) were achieved through oxidative cleavages of the double bonds in the opened C-ring.
Synthesis of ring-C modified oleanolic acid derivatives and their cytotoxic evaluation
Pattnaik, Banita,Lakshma Nayak, Vadithe,Ramakrishna, Sistla,Venkata Mallavadhani, Uppuluri
, p. 152 - 158 (2016)
Ring-C of oleanolic acid was chemically modified by treating with NBS under a variety of experimental conditions. The structures of the synthesized compounds were established by spectral analysis (1H &13C NMR and Mass). All the compounds were evaluated against a panel of five human cancer cell lines by using MTT assay. Among the tested compounds, 2 and 7 showed significant activity against breast cancer cell line, MCF-7. Most significantly, compound 7 showed several folds enhanced activity against MCF-7 cancer cell lines (IC50: 2.96?μM) than that of the parent (1) and the intermediate compound (6). Flow cytometric analysis revealed that these compounds arrested the cell cycle in G0/G1 phase and induced mitochondrial mediated apoptosis.
Triterpenoids. Part 21: Oleanolic acid azaderivatives as percutaneous transport promoters
Zaprutko, Lucjusz,Partyka, Danuta,Bednarczyk-Cwynar, Barbara
, p. 4723 - 4726 (2004)
Some new oleanolic acid derivatives with lactame and thiolactame structures in the A- or C-ring were prepared and tested as percutaneous transport promoters in vitro. Their activity was comparable with activity of N-dodecylcaprolactame (Azone). A-Thiolactame derivative of methyl oleanolate (13) was the most effective compound.
