Synthesis and biological activity of some antitumor active derivatives from glycyrrhetinic acid

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

doi:10.1016/j.ejmech.2010.09.028

Cited by 55 publications

(48 citation statements)

References 19 publications

(8 reference statements)

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“…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.…”

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confidence: 99%

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

et al. 2014

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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.

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confidence: 99%

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

et al. 2014

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“…Many GA derivatives were synthesized as antitumor agents (Csuk et al 2010;Gao et al 2010;Hu et al 2010;Chadalapaka et al 2008). We have previously demonstrated that AEGA, a GA derivative, had much stronger inhibitory effects against human leukemia K562 cells compared to the parent compound 18b-GA (Gao et al 2011).…”

Section: Discussionmentioning

confidence: 98%

Induction of apoptosis with mitochondrial membrane depolarization by a glycyrrhetinic acid derivative in human leukemia K562 cells

Gao

Kang

et al. 2012

Cytotechnology

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Glycyrrhetinic acid (GA) is the active compound in Glycyrrhizae radix, a famous traditional Chinese medicine. Recently the anticancer activity of GA became the focus of scientific interest and many GA derivatives were developed as anti-tumor lead compounds. We previously reported that AEGA, a GA derivative, has proliferation inhibition and apoptosis-inducing activity in various human tumor cells. The present study was undertaken to further investigate the molecular mechanisms involved in AEGA-induced apoptosis in human leukemia K562 cells. AEGA can inhibit the growth of K562 cells in dose- and time-dependent manners determined by the MTT assay. Induction of apoptosis was evidenced by morphological changes and biochemical markers such as cell shrinkage, chromatin condensation and DNA ladder formation. Further mechanistic analysis revealed that AEGA induced apoptosis through the collapse of mitochondrial membrane potential, the accumulation of the cytosolic cytochrome c and the activation of caspase-9 and caspase-3. The apoptosis induction by AEGA was associated with the alteration in the ratio of Bcl-2/Bax protein expression. These results suggest that AEGA may induce apoptosis through a mitochondria-mediated pathway, and might have the therapeutic value against hematological malignancies.

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“…[16,17] Amongt hese components, the primary active constituent is glycyrrhizic acid (1:( 3 b,20b)-[(2-O-bd-glucopyranuronosyl-a-d-glucopyranuronosyl)oxy]-11-oxo-12oleanen-29-oic acid), which is at riterpene saponin heavily present in the dried roots of G. glabra. [19][20][21][22] Thus, the synthesis of new synthetic derivatives with elevated antitumor activityw as the focus. However,g lycyrrhetic acid has demonstrated poor inhibitory capability when applied to different tumor cell lines in most studies.…”

Section: Introductionmentioning

confidence: 99%

“…However,g lycyrrhetic acid has demonstrated poor inhibitory capability when applied to different tumor cell lines in most studies. [19][20][21][22] Thus, the synthesis of new synthetic derivatives with elevated antitumor activityw as the focus. From the molecular structure, glycyrrhetic acid has three main functional groups:t hey are located on rings A, C, and E. Therefore, chemical modifications and skeleton transformations were also concentrated on these sites ( Figure 1).…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Biological Evaluation of Glycyrrhetic Acid Derivatives as Potential VEGFR2 Inhibitors

et al. 2017

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Vascular endothelial growth factor receptor 2 (VEGFR2) has been proven to play a major role in the regulation of tumor angiogenesis. A series of novel glycyrrhetic acid derivatives were synthesized and evaluated for their VEGFR2 inhibitory activity as well as their antiproliferative properties against four cancer cell lines (MCF-7, HeLa, HepG2, and A549). In vitro biological evaluations against these human tumor cell lines indicate that most of the prepared compounds have antiproliferative activities; compound 3 a (3β-hydroxy-30-(4-phenyl-1-piperazinyl)olean-12-ene-11,30-dione) exhibited the best inhibitory activity against MCF-7 cells, with an IC value of 1.08 μm. Compound 3 a also showed the most potent inhibitory activity against VEGFR2 tyrosine kinase, with an IC value of 0.35 μm. Docking simulations were performed with the aim of discovering the binding mode of compound 3 a, and the results indicate that 3 a could bind at the VEGFR2 active site.

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Synthesis and biological activity of some antitumor active derivatives from glycyrrhetinic acid

Cited by 55 publications

References 19 publications

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

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

Induction of apoptosis with mitochondrial membrane depolarization by a glycyrrhetinic acid derivative in human leukemia K562 cells

Synthesis and Biological Evaluation of Glycyrrhetic Acid Derivatives as Potential VEGFR2 Inhibitors

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