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

Huang, Min; Gong, Ping; Wang, Yuetong; Xie, Xiaorui; Ma, Zhuangshi; Xu, Qihao; Liu, Dan; Jing, Yongkui; Zhao, Liang

doi:10.1016/j.bioorg.2020.104187

Cited by 10 publications

(9 citation statements)

References 25 publications

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“…However, GA is poorly soluble in water with low bioavailability, and long-term use can cause hyperaldosteronism: these factors limit its application greatly. To improve the activity of GA, the structure has been modified, and good results have been achieved [21][22][23][24][25]. Simultaneously, it has been found that GA can target hepatocyte membranes [26].…”

Section: Introductionmentioning

confidence: 99%

Grafting of 18β-Glycyrrhetinic Acid and Sialic Acid onto Chitosan to Produce a New Amphipathic Chitosan Derivative: Synthesis, Characterization, and Cytotoxicity

Quan

Kong

et al. 2021

Molecules

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Chitosan is the only cationic polysaccharide found in nature. It has broad application prospects in biomaterials, but its application is limited due to its poor solubility in water. A novel chitosan derivative was synthesized by amidation of chitosan with 18β-glycyrrhetinic acid and sialic acid. The chitosan derivatives were characterized by Fourier transform infrared spectroscopy, thermogravimetric analysis, and measurement of the zeta potential. We also investigated the solubility, cytotoxicity, and blood compatibility of chitosan derivatives. 18β-glycyrrhetinic acid and sialic acid could be grafted onto chitosan molecular chains. The thermal stability of the synthesized chitosan derivatives was decreased and the surface was positively charged in water and phosphate-buffered saline. After chitosan had been modified by 18 β-glycyrrhetinic acid and sialic acid, the solubility of chitosan was improved greatly in water and phosphate-buffered saline, and percent hemolysis was <5%. Novel amphiphilic chitosan derivatives could be suitable polymers for biomedical purposes.

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Section: Introductionmentioning

confidence: 99%

Grafting of 18β-Glycyrrhetinic Acid and Sialic Acid onto Chitosan to Produce a New Amphipathic Chitosan Derivative: Synthesis, Characterization, and Cytotoxicity

Quan

Kong

et al. 2021

Molecules

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“…In addition, GA derivatives 29 and 32 featuring and anilinyl and 4-aminoperidinyl group respectively, showed potent effects toward PC-3 and MCF-7 with IC 50 < 1.0 µM. On the other hand, compounds 31, 33, and 34 were significantly effective toward PC-3 with IC 50 : 0.85, 0.78, 0.68 µM, respectively [61].…”

Section: Ring a Modified Derivativesmentioning

confidence: 93%

“…Various ring A-modified GA derivatives 18-34 (Figure 3) bearing an exocyclic α,β-unsaturated carbonyl group were prepared and found to possess cytotoxic effects toward prostate (PC-3) and breast cancer (MCF-7) with IC 50 values ranging from 0.23 to 8.9 µM [61]. Furthermore, compound 21 featuring an ethylamide group illustrated better cytotoxic effects (MCF-7: IC 50 that the number of carbons in the alkyl chain of the amide play a crucial role in the cytotoxic effects.…”

Section: Ring a Modified Derivativesmentioning

confidence: 99%

Glycyrrhetinic acid: a promising scaffold for the discovery of anticancer agents

Hussain

Ali

Hakkim

et al. 2021

Expert Opinion on Drug Discovery

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Introduction: Oleanane-type pentacyclic triterpenes named glycyrrhetinic acids (GAs) featuring a C-30 carboxylic acid group, are extracted from the licorice (Glycyrrhiza uralensis). Numerous biological properties of GA have been reported and have attracted researchers from all over the world in recent years due to the peculiar GA scaffold-based semisynthetic cytotoxic effects. Areas Covered: This review represents the applications of semisynthetic derivatives of GA for the development of future cancer treatments. Included in the review are important structural features of the semisynthetic GAs crucial for cytotoxic effects. Expert opinion: Numerous semisynthetic GA derivatives illustrated excellent cytotoxic effects toward various cancer cells. Notably the C-3 (OH) at ring A along with C 30-CO 2 H at ring E as vital structural features, make GA very appealing as a lead scaffold for medicinal chemistry, since these two groups permit the creation of further chemical diversity geared toward improved cytotoxic effects. Furthermore, numerous GA derivatives have been synthesized and indicate that compounds featuring cyanoenone moieties in ring A, or compounds having the amino group or nitrogen comprising heterocycles and hybrids thereof, illustrate more potent cytotoxicity. Furthermore, GA has a great capability to be conjugated with other anticancer molecules to synergistically enhance their combined cytotoxicity.

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“…18β-glycyrrhetinic acid (18β-GRA) is a pentacyclic triterpene derivative extracted from the natural medicine licorice (Figure 1 ). It has significant anti-inflammatory[ 4 ], anti-oxidant, anti-bacterial, and anti-proliferative effects[ 5 ]. Recent studies have shown that 18β-GRA has reliable anticancer effects on human malignant tumors, such as lung cancer[ 6 ], breast cancer[ 7 ], colon cancer, and GC.…”

Section: Introductionmentioning

confidence: 99%

18β-glycyrrhetinic acid regulates mitochondrial ribosomal protein L35-associated apoptosis signaling pathways to inhibit proliferation of gastric carcinoma cells

Yuan¹,

Yang²,

Li³

et al. 2022

WJG

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BACKGROUND Gastric carcinoma (GC) is a common gastrointestinal malignancy worldwide. Based on the cancer-related mortality, the current prevention and treatment strategies for GC still show poor clinical results. Therefore, it is important to find effective drug treatment targets. AIM To explore the mechanism by which 18β-glycyrrhetinic acid (18β-GRA) regulates mitochondrial ribosomal protein L35 (MRPL35) related signal proteins to inhibit the proliferation of GC cells. METHODS Cell counting kit-8 assay was used to detect the effects of 18β-GRA on the survival rate of human normal gastric mucosal cell line GES-1 and the proliferation of GC cell lines MGC80-3 and BGC-823. The apoptosis and cell cycle were assessed by flow cytometry. Cell invasion and migration were evaluated by Transwell assay, and cell scratch test was used to detect cell migration. Furthermore, a tumor model was established by hypodermic injection of 2.5 × 10 6 BGC-823 cells at the selected positions of BALB/c nude mice to determine the effect of 18β-GRA on GC cell proliferation, and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to detect MRPL35 expression in the engrafted tumors in mice. We used the term tandem mass tag (TMT) labeling combined with liquid chromatography–tandem mass spectrometry to screen for differentially expressed proteins (DEPs) extracted from GC cells and control cells after 18β-GRA intervention. A detailed bioinformatics analysis of these DEPs was performed, including Gene Ontology annotation and enrichment analysis, Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, and so on. Moreover, STRING database ( ) was used to predict protein-protein interaction (PPI) relationships and Western blot was used to detect the expression of proteins of interest in GC cells. RESULTS The results indicated that 18β-GRA could inhibit the proliferation of GC cells in a dose- and time-dependent manner. It could induce GC cell apoptosis and arrest the cell cycle at G0/G1 phase. The proportion of cells arrested at S phase decreased with the increase of 18-GRA dose, and the migration and invasiveness of GC cells were inhibited. The results of animal experiments showed that 18β-GRA could inhibit tumor formation in BALB/c nude mice, and qRT-PCR results showed that MRPL35 expression level was significantly reduced in the engrafted tumors in mice. Using TMT technology, 609 DEPs, among which 335 were up-regulated and 274 were down-regulated, were identified in 18β-GRA intervention compared with control. We found that the intervention of 18β-GRA in GC cells involved many important biological processes and signaling pathways, such as cellular processes, biological regulation, and TP53 signaling pathway. Notably, after the drug intervention, MRPL35 expression was significantly down-regulated ( ...

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

Cited by 10 publications

References 25 publications

Grafting of 18β-Glycyrrhetinic Acid and Sialic Acid onto Chitosan to Produce a New Amphipathic Chitosan Derivative: Synthesis, Characterization, and Cytotoxicity

Grafting of 18β-Glycyrrhetinic Acid and Sialic Acid onto Chitosan to Produce a New Amphipathic Chitosan Derivative: Synthesis, Characterization, and Cytotoxicity

Glycyrrhetinic acid: a promising scaffold for the discovery of anticancer agents

18β-glycyrrhetinic acid regulates mitochondrial ribosomal protein L35-associated apoptosis signaling pathways to inhibit proliferation of gastric carcinoma cells

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