Does One Keto Group Matter? Structure‐Activity Relationships of Glycyrrhetinic Acid Derivatives Modified at Position C‐11

Csuk, René; Schwarz, Štefan; Kluge, Ralph; Ströhl, Dieter

doi:10.1002/ardp.201000327

Cited by 9 publications

(3 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Of these compounds, 28 , which possesses a methyl ester group, was the most active, with a MIC value that was 5-fold lower than that of the positive control. Csuk et al found no direct relationship between the C-11 ketone group and the apoptotic activity of compound 1 derivatives . However, in the present study, a significant difference in bacterial inhibition activity was observed between the 11-oxo and 11-deoxo compounds.…”

Section: Resultscontrasting

confidence: 76%

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

Huang

Hao

et al. 2016

J. Nat. Prod.

View full text Add to dashboard Cite

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.

show abstract

Section: Resultscontrasting

confidence: 76%

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

Huang

Hao

et al. 2016

J. Nat. Prod.

View full text Add to dashboard Cite

show abstract

“…Recently, GA attracted the focus of research interests not only for it can be accessed abundantly from the roots of licorice [up to 24% (7,8)], but also for its triggering apoptosis on tumor cells (9)(10)(11)(12). However, GA has only weak inhibitory effect against various tumor cell lines (IC 50 is approximately 80 lM), and some structural modifications have been previously performed (13)(14)(15)(16)(17)(18)(19)(20). We also become interested in producing more active GA analogs.…”

mentioning

confidence: 99%

Synthesis of Novel Heterocyclic Ring‐Fused 18β‐Glycyrrhetinic Acid Derivatives with Antitumor and Antimetastatic Activity

et al. 2014

View full text Add to dashboard Cite

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 IC50 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.

show abstract

“…The studies on structural modifications at ring-C were mainly focused on the carbonyl function located at C-11. According to Fiore and Salvi [ 48 , 49 ], a ketone group at position C-11 was the primary cause for the apoptotic activity of GA derivatives, but the research conducted by Csuk et al [ 50 ] showed that there was no direct relation between the presence of the C-11 ketone group and the apoptotic activity of the compounds. Also, esterification at C-30 was important, as mentioned above.…”

Section: Four Aspects Of the Structural Modifications Of Glycyrrhementioning

confidence: 99%

An Overview of Structurally Modified Glycyrrhetinic Acid Derivatives as Antitumor Agents

Zhang

et al. 2017

Molecules

View full text Add to dashboard Cite

Glycyrrhetinic Acid (GA), a triterpenoid aglycone component of the natural product glycyrrhizinic acid, was found to possess remarkable anti-proliferative and apoptosis-inducing activity in various cancer cell lines. Though GA was not as active as other triterpenes, such as betulinic acid and oleanolic acid, it could trigger apoptosis in tumor cells and it can be obtained easily and cheaply, which has stimulated scientific interest in using GA as a scaffold to synthesize new antitumor agents. The structural modifications of GA reported in recent decades can be divided into four groups, which include structural modifications on ring-A, ring-C, ring-E and multiple ring modifications. The lack of a comprehensive and recent review on this topic prompted us to gather more new information. This overview is dedicated to summarizing and updating the structural modification of GA to improve its antitumor activity published between 2005 and 2016. We reviewed a total of 210 GA derivatives that we encountered and compiled the most active GA derivatives along with their activity profile in different series. Furthermore, the structure activity relationships of these derivatives are briefly discussed. The included information is expected to be of benefit to further studies of structural modifications of GA to enhance its antitumor activity.

show abstract

Does One Keto Group Matter? Structure‐Activity Relationships of Glycyrrhetinic Acid Derivatives Modified at Position C‐11

Cited by 9 publications

References 18 publications

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

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

Synthesis of Novel Heterocyclic Ring‐Fused 18β‐Glycyrrhetinic Acid Derivatives with Antitumor and Antimetastatic Activity

An Overview of Structurally Modified Glycyrrhetinic Acid Derivatives as Antitumor Agents

Contact Info

Product

Resources

About