Browse
Submit Data
Databases
API
Help

Dataset Information

39 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Efficient synthesis of piperazinyl amides of 18β-glycyrrhetinic acid.

ABSTRACT: In the present study, a practical method to prepare piperazinyl amides of 18β-glycyrrhetinic acid was developed. Two main procedures for the construction of important intermediate 8 are discussed. One procedure involves the amidation of 1-Boc-piperazine with 3-acetyl-18β-glycyrrhetinic acid, prepared by the reaction of 18β-glycyrrhetinic acid with acetic anhydride without any solvent at 130 °C. The other procedure to prepare compound 8 involves the amidation of 18β-glycyrrhetinic acid followed by the esterification with acetic anhydride. Finally, compound 8 underwent N-Boc deprotection to prepare product 4. To ascertain the scope of the reaction, another C-3 ester derivative 17 was tested under the optimized reaction conditions. Furthermore, the reasons for the appearance of byproducts were elucidated. Crystallographic data of a selected piperazinyl amide is reported.

SUBMITTER: Cai D

PROVIDER: S-EPMC7188925 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Efficient synthesis of piperazinyl amides of 18β-glycyrrhetinic acid.

Cai Dong D Zhang ZhiHua Z Meng Yufan Y Zhu KaiLi K Chen LiYi L Yu ChangXiang C Yu ChangWei C Fu ZiYi Z Yang DianShen D Gong YiXia Y

Beilstein journal of organic chemistry 20200421

In the present study, a practical method to prepare piperazinyl amides of 18β-glycyrrhetinic acid was developed. Two main procedures for the construction of important intermediate 8 are discussed. One procedure involves the amidation of 1-Boc-piperazine with 3-acetyl-18β-glycyrrhetinic acid, prepared by the reaction of 18β-glycyrrhetinic acid with acetic anhydride without any solvent at 130 °C. The other procedure to prepare compound 8 involves the amidation of 18β-glycyrrhetinic a ...[more]

PMID: 32395183

Similar Datasets

18β-glycyrrhetinic Acid Modulated Autophagy is Cytotoxic to Breast Cancer Cells.

Project description:The development of endocrine therapy resistance in the luminal A subtype of breast cancer is related to the appearance of protective autophagy. The bioactive component from the root of licorice, 18β-glycyrrhetinic acid (18β-GA), has many antitumor properties. Whether 18β-GA can modulate autophagy to inhibit proliferation of the luminal A subtype is still unclear. The proportion of apoptosis caused by 18β-GA in MCF-7 and T-47D cells was determined using flow cytometry. The autophagy marker, LC3-II conversion, was investigated using Western blotting, and a PremoTM Tandem Autophagy Sensor Kit. We found that the concentration (150-μM) of 18β-GA caused caspase-dependent apoptosis and LC3-II accumulation or blocked autophagic flux. Moreover, 18β-GA-mediated apoptosis was improved using rapamycin but reversed by 3-methyladenine (3-MA) addition. The phosphorylation level of Jun-amino-terminal kinase (JNK) was increased significantly in the 18β-GA treatment and combined incubation using rapamycin. A JNK inhibitor (SP600125) significantly inhibited 18β-GA-mediated apoptosis, LC3-II accumulation and rescued the numbers of MCF-7 and T-47D colony formation. Especially, 18β-GA can inhibit xenograft tumor growth in BALB/c nude mice. These data indicate the combination of 18β-GA with rapamycin or 3-MA can sensitize or decrease MCF-7 and T-47D cells to 18β-GA-induced apoptosis, respectively. 18β-GA modulated autophagy is cytotoxic to luminal A subtype breast cancer cells through apoptosis promotion and JNK activation.

| S-EPMC10087636 | biostudies-literature

Charge-transfer interaction mediated organogels from 18β-glycyrrhetinic acid appended pyrene.

Project description:We describe herein the two-component charge-transfer (CT) interaction induced organogel formation with 18β-glycyrrhetinic acid appended pyrene (GA-pyrene, 3) as the donor, and 2,4,7-trinitrofluorenone (TNF, 4) as the acceptor. The use of TNF (4) as a versatile electron acceptor in the formation of CT gels is demonstrated through the formation of gels in a variety of solvents. Thermal stability, stoichiometry, scanning electron microscopy (SEM), optical micrographs, and circular dichroism (CD) are performed on these CT gels to investigate their thermal and assembly properties. UV-vis, fluorescence, mass spectrometric as well as variable-temperature (1)H NMR experiments on these gels suggest that the CT interaction is one of the major driving forces for the formation of these organogels.

| S-EPMC3869347 | biostudies-literature

Synthesis and discovery of 18β-glycyrrhetinic acid derivatives inhibiting cancer stem cell properties in ovarian cancer cells.

Project description:Despite advances in ovarian cancer treatment, the five-year overall survival rate is less than 30% with the presence of cancer stem cells (CSCs). To develop CSC-targeting therapy, a series of 18β-glycyrrhetinic acid (GA) derivatives containing cinnamamide moiety have been designed, synthesized, and screened for their antiproliferative activity in SKOV3 and OVCAR3 cells. Most of the compounds exhibited stronger antiproliferative activity than GA, and compound 7c was the most active one. Further biological studies showed that compound 7c could induce apoptosis and suppress migration. In addition, compound 7c could not only observably decrease the colony formation and sphere formation ability, but also significantly reduce the CD44+, CD133+, and ALDH+ subpopulation in SKOV3 and OVCAR3 cells. In conclusion, these results indicate that compound 7c is a promising anti-CSC agent for further anti-ovarian cancer studies.

| S-EPMC9070660 | biostudies-literature

Design, synthesis and biological evaluation of novel amide-linked 18β-glycyrrhetinic acid derivatives as novel ALK inhibitors.

Project description:A series of novel amide-linked 18β-glycyrrhetinic acid derivatives were developed by incorporating substituted piperazine amide fragments into the C30-COOH of 18β-glycyrrhetinic acid scaffold. The synthesized compounds were evaluated for their anticancer activity against Karpas299, A549, HepG2, MCF-7, and PC-3 cell lines by MTT assay. Besides, some compounds with electron-withdrawing groups on phenyl moieties exhibited noticeable antiproliferative activity. The most potent compound 4a was also found to be non-toxic to normal human hepatocytes LO2 cells. The compound 4a exhibited moderate inhibitory activity against wild-type ALK with an IC50 value of 203.56 nM and relatively weak potent activity to c-Met (IC50 > 1000 nM). Molecular docking studies were performed to explore the diversification in bonding patterns between the compound 4a and Crizotinib.

| S-EPMC9050490 | biostudies-literature

Pharmacological Features of 18β-Glycyrrhetinic Acid: A Pentacyclic Triterpenoid of Therapeutic Potential.

Project description:Glycyrrhiza glabra L. (belonging to the family Leguminosae), commonly known as Licorice, is a popular medicinal plant that has been used in traditional medicine worldwide for its ethnopharmacological efficacy in treating several ailments. Natural herbal substances with strong biological activity have recently received much attention. The main metabolite of glycyrrhizic acid is 18β-glycyrrhetinic acid (18βGA), a pentacyclic triterpene. A major active plant component derived from licorice root, 18βGA has sparked a lot of attention due to its pharmacological properties. The current review thoroughly examines the literature on 18βGA, a major active plant component obtained from Glycyrrhiza glabra L. The current work provides insight into the pharmacological activities of 18βGA and the potential mechanisms of action involved. The plant contains a variety of phytoconstituents such as 18βGA, which has a variety of biological effects including antiasthmatic, hepatoprotective, anticancer, nephroprotective, antidiabetic, antileishmanial, antiviral, antibacterial, antipsoriasis, antiosteoporosis, antiepileptic, antiarrhythmic, and anti-inflammatory, and is also useful in the management of pulmonary arterial hypertension, antipsychotic-induced hyperprolactinemia, and cerebral ischemia. This review examines research on the pharmacological characteristics of 18βGA throughout recent decades to demonstrate its therapeutic potential and any gaps that may exist, presenting possibilities for future drug research and development.

| S-EPMC10005454 | biostudies-literature

Synthesis, molecular docking, and biological evaluation of [3,2-b]indole fused 18β-glycyrrhetinic acid derivatives against skin melanoma.

Project description:Melanoma, the most serious yet uncommon type of cancer, originates in melanocytes. Risk factors include UV radiation, genetic factors, tanning lamps and beds. Here, we described the synthesis and selective anti melanoma activity of [3,2-b]indole fused 18β-glycyrrhetinic acid, a derivative of 18β-glycyrrhetinic acid in murine B16F10 and A375 human melanoma cell lines. Among the 14 molecules, GPD-12 showed significant selective cytotoxic activity against A375 and B16F10 cell lines with IC50 of 13.38 μM and 15.20 μM respectively. GPD 12 induced the formation of reactive oxygen species in A375 cells that could trigger oxidative stress mediated cell death as is evident from the increased expression of apoptosis related proteins such as caspase-9 and caspase-3 and the increased ratio of Bax to Bcl2. The results showed that GPD 12 can be used as an effective therapeutic agent against melanoma.

| S-EPMC10086573 | biostudies-literature

Amelioration effect of 18β-Glycyrrhetinic acid on methylation inhibitors in hepatocarcinogenesis -induced by diethylnitrosamine.

Project description:Aimsuppression of methylation inhibitors (epigenetic genes) in hepatocarcinogenesis induced by diethylnitrosamine using glycyrrhetinic acid.MethodIn the current work, we investigated the effect of sole GA combined with different agents such as doxorubicin (DOX) or probiotic bacteria (Lactobacillus rhamanosus) against hepatocarcinogenesis induced by diethylnitrosamine to improve efficiency. The genomic DNA was isolated from rats' liver tissues to evaluate either methylation-sensitive or methylation-dependent resection enzymes. The methylation activity of the targeting genes DLC-1, TET-1, NF-kB, and STAT-3 was examined using specific primers and cleaved DNA products. Furthermore, flow cytometry was used to determine the protein expression profiles of DLC-1 and TET-1 in treated rats' liver tissue.ResultsOur results demonstrated the activity of GA to reduce the methylation activity in TET-1 and DLC-1 by 33.6% and 78%, respectively. As compared with the positive control. Furthermore, the association of GA with DOX avoided the methylation activity by 88% and 91% for TET-1 and DLC-1, respectively, as compared with the positive control. Similarly, the combined use of GA with probiotics suppressed the methylation activity in the TET-1 and DLC-1 genes by 75% and 81% for TET-1 and DLC-1, respectively. Also, GA and its combination with bacteria attenuated the adverse effect in hepatocarcinogenesis rats by altering potential methylomic genes such as NF-kb and STAT3 genes by 76% and 83%, respectively.ConclusionGA has an ameliorative effect against methylation inhibitors in hepatocellular carcinoma (HCC) by decreasing the methylation activity genes.

| S-EPMC10844948 | biostudies-literature

18β-Glycyrrhetinic-acid-mediated unfolded protein response induces autophagy and apoptosis in hepatocellular carcinoma.

Project description:18β-Glycyrrhetinic acid (GA) is the active ingredient of the traditional Chinese medicine, Glycyrrhrzae Radix et Rhizoma. Here, we explored the effects of GA on hepatocellular carcinoma (HCC) in vitro and in vivo and the underlying molecular mechanisms. We confirmed that GA suppressed proliferation of various HCC cell lines. Treatment of GA caused G0/G1 arrest, apoptosis and autophagy in HCC cells. GA-induced apoptosis and autophagy were mainly due to the unfolded protein response. We compared the roles of the ATF4/CHOP and IRE1α/XBP1s UPR pathways, which were both induced by GA. The ATF4/CHOP cascade induced autophagy and was indispensable for the induction of apoptosis in GA-treated HCC cells. In contrast, the IRE1α/XBP1s cascade protected HCC cells from apoptosis in vitro and in vivo induced by GA. Despite this, activation of autophagy protected HCC cells from apoptosis induced by GA. We concluded that pharmacological inhibition of autophagy or IRE1α may be of benefit to enhance the antitumor activity of GA.

| S-EPMC6008326 | biostudies-literature

18β-glycyrrhetinic acid suppresses gastric cancer by activation of miR-149-3p-Wnt-1 signaling.

Project description:18β-glycyrrhetinic acid (GRA) exerts anti-tumor effects on various types of cancer. In the present study, we found that GRA attenuated the severity of gastritis and suppressed gastric tumorigenesis in transgenic mice. We also discovered that miR-149-3p was downregulated in gastric cancer tissues and cell lines as compared to normal gastric tissues and epithelial cells, but was upregulated by GRA. miR-149-3p expression also correlated negatively with lymphnode metastasis. Our functional assays showed that miR-149-3p overexpression inhibited cell proliferation and cell cycle progression while inducing apoptosis, while inhibition of miR-149-3p had the opposite effects. In addition, we identified Wnt-1 as a direct target of miR-149-3p. These data suggest that GRA inhibits the initiation and progression of gastric tumors by ameliorating the inflammatory microenvironment through downregulation of COX-2 expression and by inhibiting Wnt-1 expression through the upregulation of tumor suppressor miR-149-3p. GRA may thus have the potential to serve as a useful therapeutic agent for the prevention and treatment of gastric cancer.

| S-EPMC5342136 | biostudies-literature

In silico and in vivo anti-malarial studies of 18β glycyrrhetinic acid from Glycyrrhiza glabra.

Project description:Malaria is one of the most prevailing fatal diseases causing between 1.2 and 2.7 million deaths all over the world each year. Further, development of resistance against the frontline anti-malarial drugs has created an alarming situation, which requires intensive drug discovery to develop new, more effective, affordable and accessible anti-malarial agents possessing novel modes of action. Over the past few years triterpenoids from higher plants have shown a wide range of anti-malarial activities. As a part of our drug discovery program for anti-malarial agents from Indian medicinal plants, roots of Glycyrrhizaglabra were chemically investigated, which resulted in the isolation and characterization of 18β-glycyrrhetinic acid (GA) as a major constituent. The in vitro studies against P. falciparum showed significant (IC50 1.69 µg/ml) anti-malarial potential for GA. Similarly, the molecular docking studies showed adequate docking (LibDock) score of 71.18 for GA and 131.15 for standard anti-malarial drug chloroquine. Further, in silico pharmacokinetic and drug-likeness studies showed that GA possesses drug-like properties. Finally, in vivo evaluation showed a dose dependent anti-malarial activity ranging from 68-100% at doses of 62.5-250 mg/kg on day 8. To the best of our knowledge this is the first ever report on the anti-malarial potential of GA. Further work on optimization of the anti-malarial lead is under progress.

| S-EPMC3782471 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data