1321990-56-0

Upstream product

• 6184-16-3 3,11-dioxoolean-12-en-30-oic acid 
• 100-39-0 benzyl bromide 
• 100-51-6 benzyl alcohol 
• 51984-75-9 benzyl (2S,4aS,6aS,6bR,8aR,10S,12aS,12bR,14bR)-10-hydroxy-2,4a,6a,6b,9,9,12a-heptamethyl-13-oxo-1,2,3,4,4a,5,6,6a,6b,7,8,8a,9,10,11,12,12a,12b,13,14b-icosahydropicene-2-carboxylate 
• 471-53-4 enoxolone 

Relevant academic research and scientific papers

The synthesis of glycyrrhetinic acid derivatives containing a nitrogen heterocycle and their antiproliferative effects in human leukemia cells

Fifteen novel glycyrrhetinic acid derivatives containing a nitrogen heterocycle at C-30 and with different A-ring substituents were designed and synthesized. All of these derivatives have improved antiproliferative effects against human HL-60 leukemia cells. Compounds with a cyano-enone functionality on the A-ring exhibit greater growth inhibitory effects, compared to those with a 2-hydroxymethylene-3-keto, an isoxazole, or a 2-cyano-3-keto group. N-(2-cyano-3,11-dioxoolean-1,12-dien-30-yl)-4-piperidyl piperidine (9b) was found to be two-fold more potent than methyl 2-cyano-3,11-dioxooleana-1,12-dien- 30-oate (CDODO-Me-11).

Synthesis of novel heterocyclic ring-fused 18β-glycyrrhetinic acid derivatives with antitumor and antimetastatic activity

Glycyrrhetinic acid (GA) is one of the most important triterpenoic acids shows many pharmacological effects, especially antitumor activity. GA triggers apoptosis in various tumor cell lines. However, the antitumor activity of GA is weak, thus the synthesis of new synthetic analogs with enhanced potency is needed. By introducing various five-member fused heterocyclic rings at C-2 and C-3 positions, 18 novel GA derivatives were obtained. These compounds were evaluated for their inhibitory activity against the growth of eight different tumor cell lines using a SRB assay. The most active compound 37 showed IC 50 between 5.19 and 11.72 μm, which was about 11-fold more potent than the lead compound GA. An apoptotic effect of GA and 37 was determined using flow cytometry and trypan blue exclusion assays. We also demonstrated here for the first time that GA and the synthetic derivatives exhibited inhibitory effect on migration of the tested tumor cells, especially 37 which was about 20-fold more potent than GA on antimetastatic activity.

Sulfonamides 18 β - glycyrrhetinic acid derivatives and preparation method and application thereof

The invention provides a sulfonamides 18 β - glycyrrhetinic acid derivative as well as a preparation method and application thereof. Belong to medicine technical field. To the invention, the series of derivatives of 18 β - glycyrrhetinic acid modified by sulfonamide groups is designed and synthesized. By introducing an active sulfonamide group, the water solubility and the bioavailability of the compound can be significantly improved to improve the antitumor activity of the related derivative. Experiments prove that the compound 6a has excellent cytotoxic activity for 3 human cancer cells (MCF - 7, A549, HEPG2), is far higher than the parent drug GA, and the activity of the compound 6a in comparison with the positive control anti-cancer drug gefitinib is remarkably improved. The compound is expected to be a prodrug for replacing gefitinib. The drug resistance of the cancer patients to gefitinib can be solved. Thus, the utility model has good practical application value.

Synthesis and antitumor effects of novel 18β-glycyrrhetinic acid derivatives featuring an exocyclic α,β-unsaturated carbonyl moiety in ring A

A series of novel 18β-glycyrrhetinic acid (GA) derivatives featuring an exocyclic α,β-unsaturated carbonyl moiety in ring A were synthesized and evaluated for their antitumor activities. Compounds 5c and 5l showed stronger cytotoxicity than other compounds and reported GA analogue CDODA-Me (methyl 2-cyano-3,11-dioxo-18β-olean-1,12-dien-30-oate). 5c and 5l induced apoptosis in cancer cells accompanying with c-Flip reduction and Noxa induction, associated with decreased HDAC3 expression and increased acetylation of H3. 5l displayed better stability properties than 5c and CDODA-Me in microsomes and plasma, 5l also showed favorable pharmacokinetic profiles and inhibited tumor growth in mice. Compound 5l represents a new type of GA derivatives with improved antitumor activity.

Synthesis and biological activity of glycyrrhetinic acid derivatives as antitumor agents

Glycyrrhetinic acid (GA) had been the star anticancer lead compound and appealed to many scientists all over the world; however, its antitumor activity was not potent enough. To improve GA's cytoxicity and explore the effect of bonding mode on antitumor activity, 32 compounds including GA-OH series (GO, esters in C-3 position) and GA-NH2 series (GN, with amide linkages in C-3 position) had been designed and synthesized. All the compounds were screened for in vitro cytotoxicity against A549, HepG2, MCF-7, Hela and MDCK cell lines. As a result, all the de-protected (without Boc group) derivatives showed much stronger cytotoxic activity than GA, and surprisingly enough, all the GN series of the compounds were more potent than GO series against various tumor cells. Among them, the compound 26 (amide linkages in C-3 position) exhibited stronger antitumor activity against A549 cell line (IC50 = 2.109 ± 0.11 μM) than the positive drug cisplatin (IC50 = 9.001 ± 0.37 μM). Further studies indicated that compound 26 could induce A549 apoptosis via nuclei fragmentation. The detection of apoptosis and cell cycle analysis indicated that compound 26 could induce the early apoptosis and prevent A549 cells transition from S to G2 phase. Furthermore, the structure-activity relationships were briefly discussed. Among which, current study displayed amide linkages in C-3 position could effectively enhance GA cytotoxicity, providing a new modification strategy for further study.

2-substituted-18beta-glycyrrhetic acid derivative and application thereof

The invention belongs to the technical field of medicine, and specifically relates to a 18beta-glycyrrhetic acid derivative and an opticalisomeride and a salt acceptable pharmaceutically thereof. According to a preparation method of the derivative, a medicine composition with the derivative as an active component is used for preparing drugs treating and/or preventing cancers. The derivative as shown in a general formula I, the opticalisomeride and the salt acceptable pharmaceutically have the following structure, wherein each variable is as shown in the claims and the description. The formulaI is shown in the description.

18β-Glycyrrhetinic Acid Derivatives Possessing a Trihydroxylated A Ring Are Potent Gram-Positive Antibacterial Agents

The oleanane-type triterpene 18β-glycyrrhetinic acid (1) was modified chemically through the introduction of a trihydroxylated A ring and an ester moiety at C-20 to enhance its antibacterial activity. Compounds 22, 23, 25, 28, 29, 31, and 32 showed more potent inhibitory activity against Streptomyces scabies than the positive control, streptomycin. Additionally, the inhibitory activity of the most potent compound, 29, against Bacillus subtilis, Staphylococcus aureus, and methicillin-resistant Staphylococcus aureus was greater than that of the positive controls. The antibacterial mode of action of the active derivatives involved the regulation of the expression of genes associated with peptidoglycans, the respiratory metabolism, and the inherent virulence factors found in bacteria, as determined through a quantitative real-time reverse transcriptase PCR assay.

DERIVATIVE OF 18beta-GLYCYRRHETINIC ACID APT TO SUPPRESS CANCER CELLS

The present invention is correlated with a derivative of 18β-glycyrrhetinic acid apt to suppressing cancer cells, which is selected from a group comprising of structure I and structure II: wherein residue R1 is selected from one of CH3 and CH2C6H5, residue R2 is selected from one of COOCH3, COOCH2CH3, COOCH(CH3)2, CONHCH2CH3, CONHCH2CH2CH3, and CONHCH2(CH3)2, and residue R3 is selected from one of COOCH2CH3, COOCH(CH3)2, CONHCH2CH3, CONHCH2CH2CH3, and CONHCH2(CH3)2.

18β-Glycyrrhetinic acid derivatives induced mitochondrial-mediated apoptosis through reactive oxygen species-mediated p53 activation in NTUB1 cells

Twenty six 18β-glycyrrhetinic acid (GA) (1) derivatives 2-27 including twelve new GA derivatives 10, 11, 13-17, 21-25 were synthesized and evaluated for cytotoxicities against NTUB1 cells (human bladder cancer cell lines). seco-Compounds 9, 25, and 27 are the most potent compounds of this series, inhibiting cell growth of human NTUB1 cells with an IC50 values of 2.34 ± 0.28, 4.76 ± 1.15, and 3.31 ± 0.61 μM, respectively. Exposure of NTUB1 to 25 for 24 h significantly increased the production of reactive oxygen species (ROS). Flow cytometric analysis exhibited that treatment of NTUB1 with 25 did not induce cell cycle arrest but accompanied by an increase of apoptotic cell death in a dose-dependant manner after 24 h. Mitochondrial membrane potential (MMP) decreased significantly in a dose-dependant manner when the NTUB1 cells were exposed to 25 for 24 h. Marked collapse of the MMP suggested that dysfunction of the mitochondria may be involved in the oxidative burst and apoptosis induced by 25. Western blot analysis shows that NTUB1 cells treated with 25 increased the level of p-p53 in a dose-dependant manner. Further, NAC treatment prevented p53 phosphorylation stimulated by 25. These results suggested that 25 induced a mitochondrial- mediated apoptosis in NTUB1 cells through activation of p53, which are mainly mediated ROS generated by 25.