471-53-4Relevant articles and documents
Glycyrrhiza glabra extract and quercetin reverses cisplatin resistance in triple-negative MDA-MB-468 breast cancer cells via inhibition of cytochrome P450 1B1 enzyme
Sharma, Rajni,Gatchie, Linda,Williams, Ibidapo S.,Jain, Shreyans K.,Vishwakarma, Ram A.,Chaudhuri, Bhabatosh,Bharate, Sandip B.
, p. 5400 - 5403 (2017)
The development of multi-drug resistance to existing anticancer drugs is one of the major challenges in cancer treatment. The over-expression of cytochrome P450 1B1 enzyme has been reported to cause resistance to cisplatin. With an objective to discover cisplatin-resistance reversal agents, herein, we report the evaluation of Glycyrrhiza glabra (licorice) extracts and its twelve chemical constituents for inhibition of CYP1B1 (and CYP1A1) enzyme in Sacchrosomes and live human cells. The hydroalcoholic extract showed potent inhibition of CYP1B1 in both Sacchrosomes as well as in live cells with IC50 values of 21 and 16 μg/mL, respectively. Amongst the total of 12 constituents tested, quercetin and glabrol showed inhibition of CYP1B1 in live cell assay with IC50 values of 2.2 and 15 μM, respectively. Both these natural products were found to be selective inhibitors of CYP1B1, and does not inhibit CYP2 and CYP3 family of enzymes (IC50 > 20 μM). The hydroalcoholic extract of G. glabra and quercetin (4) showed complete reversal of cisplatin resistance in CYP1B1 overexpressing triple negative MDA-MB-468 breast cancer cells. The selective inhibition of CYP1B1 by quercetin and glabrol over CYP2 and CYP3 family of enzymes was studied by molecular modeling studies.
Oleanane-type triterpene glucuronides from the roots of Glycyrrhiza uralensis Fischer
Zheng, Yun-Feng,Qi, Lian-Wen,Cui, Xiao-Bing,Peng, Guo-Ping,Peng, Yong-Bo,Ren, Mei-Ting,Cheng, Xiao-Lan,Li, Ping
, p. 1457 - 1463 (2010)
Investigation of characteristic constituents of the roots of Glycyrrhiza uralensis Fischer led to isolation of four new triterpene glucuronides, namely uralsaponins CF (1-4), an artificial product, namely the methyl ester of glycyrrhizin (5), as well as six known triterpene glucuronides (6-11). These new compounds were identified by 1D and 2DNMR spectroscopic analysis. The cytotoxicity of the selected compounds and their aglycones were evaluated against HeLa and MCF-7 cancer cell lines, and the preliminary structure-activity relationship was also elucidated.
3-(2,6-Dichloro-benzyloxy)-11-oxo-olean-12-ene-29-oic acid, a semisynthetic derivative of glycyrrhetic acid: Synthesis, antiproliferative, apoptotic and anti-angiogenesis activity
Sharma, Rajni,Guru, Santosh K.,Jain, Shreyans K.,Pathania, Anup Singh,Vishwakarma, Ram A.,Bhushan, Shashi,Bharate, Sandip B.
, p. 564 - 575 (2015)
Glycyrrhetic acid (2, 3β-hydroxyl-11-oxo-olean-12-ene-29-oic acid), a pentacyclic triterpenoid isolated from Glycyrrhiza glabra, is known to possess a wide range of biological activities. Herein, we report the synthesis and antiproliferative activity of 3-O-ether derivatives of glycyrrhetic acid. The cytotoxicity of the prepared derivatives was investigated in three cancer cell lines, including human pancreatic (MIAPaCa-2), prostate (PC-3) and human hepatocellular liver carcinoma (HepG-2). Amongst the tested compounds, the 2,6-dichlorobenzyl 5b and 2,4-dichlorobenzyl derivative 5r displayed significant cytotoxicity in PC-3 cells with IC50 values of 6 and 18 μM, respectively. The dichlorobenzyl derivative 5b also displayed cytotoxicity in MIAPaCa-2 (IC50: 7 μM) and HepG-2 cells (IC50: 19 μM). Further, compound 5b was investigated for apoptosis-induction by cell cycle analysis, nuclear morphological changes and mitochondrial membrane potential loss in PC-3 cells. Compound 5b led to an increase in the sub-G1 population in PC-3 cells, which is indicative of its apoptotic properties. Interestingly, compound 5b also arrested the S-phase of the cell cycle. The nuclear morphology of PC-3 cells after treatment with compound 5b was also investigated which confirmed the formation of apoptotic bodies. Compound 5b induced apoptosis through both intrinsic and extrinsic apoptotic pathways in PC-3 cells, which was confirmed by mitochondrial membrane potential loss, inhibition of pro-caspase-3, 8 and 9 and cleavage of PARP-1. Furthermore, there was a significant decrease in the Bcl-2/Bax ratio induced by compound 5b in PC-3 cells. Interestingly, compound 5b also inhibited the VEGF-induced PC-3 cell migration and decreased the wound closure percentage from 100 to 12% at 30 μM. Similarly, compound 5b inhibited the angiogenesis-dependent cell migration in HUVEC cells and decreased wound closure from 100 to 20% at 30 μM, indicating its anti-angiogenic activity. This journal is
Self-assembly of a renewable nano-sized triterpenoid 18β-glycyrrhetinic acid
Bag, Braja Gopal,Majumdar, Rakhi
, p. 8623 - 8626 (2012)
The nano-sized triterpenoid 18β-glycyrrhetinic acid extractable from Glycyrrhiza glabra self assembled in different liquids affording mostly nano to microsized spherical and flower like objects consisting of fibrillar networks yielding thermoreversible gels. The self-assemblies have been utilized for the templated growth of CdS nanoparticles.
Application of bacterial directed enzyme prodrug therapy as a targeted chemotherapy approach in a mouse model of breast cancer
Bahrami, Ahmad Reza,Hosseini-Giv, Niloufar,Matin, Maryam M.
, (2021/08/03)
Cancer is the second leading cause of death in the world. Some of the usual cancer treatments include surgery, chemotherapy, and radiotherapy. However, due to low efficacy and side effects of these treatments, novel targeted therapeutic methods are needed. One of the common drawbacks of cancer chemotherapy is off-target toxicity. In order to overcome this problem, many investigations have been conducted. One of the new targeted therapy methods known as bacterial directed enzyme-prodrug therapy (BDEPT) employs bacteria as enzyme carriers to convert a pro-drug to a drug specifically within the tumor site. In the present study, we used Escherichia coli DH5α carrying luxCDABE gene cluster and overexpressing β-glucuronidase for luminescent emission and enzyme expression, respectively. Enzyme expression can lead to the conversion of glycyrrhizic acid as a prodrug to glycyrrhetinic acid, a potent anti-cancer agent. DH5α-lux/βG was characterized and its stability was also evaluated. Bacteria colonization in the tumor site was measured by tissue homogenate preparation and colony counting method. Histopathological studies on the liver, spleen, and tumor were also conducted. According to the results, co-treatment of 4T1, a highly metastatic mouse breast cancer cell line, with GL and DH5α-lux/βG could significantly decrease the IC50 values. Moreover, increased number of bacteria could lead to a dramatic drop in IC50 value. Specific colonization of DH5α-lux/βG was observed in the tumor site compared with other tissues (p 0.0001). Moreover, the biocompatibility evaluation proved that DH5α-lux/βG had no adverse effects on normal tissues. Furthermore, concurrent usage of GL and bacteria in the treatment of induced 4T1 tumors in BALB/c mice significantly delayed tumor growth (p0.001) during 16 days of investigation. Based on these findings, BDEPT might be useful for targeted breast cancer therapy, although further investigations are required to confirm this.
2D- and 3D-QSAR modelling, molecular docking and in vitro evaluation studies on 18β-glycyrrhetinic acid derivatives against triple-negative breast cancer cell line
Shukla, Aparna,Tyagi, Rekha,Meena, Sanjeev,Datta, Dipak,Srivastava, Santosh Kumar,Khan, Feroz
, p. 168 - 185 (2019/03/07)
Triple-negative breast cancers (TNBCs) are one of the most aggressive and complex forms of cancers in women. TNBCs are commonly known for their complex heterogeneity and poor prognosis. The present work aimed to develop a predictive 2D and 3D quantitative structure–activity relationship (QSAR) models against metastatic TNBC cell line. The 2D-QSAR was based on multiple linear regression analysis and validated by Leave-One-Out (LOO) and external test set prediction approach. QSAR model presented regression coefficient values for training set (r2), LOO-based internal regression (q2) and external test set regression (pred_r2) which are 0.84, 0.82 and 0.75, respectively. Five properties, Epsilon4 (electronegativity), ChiV3cluster (valence molecular connectivity index), chi3chain (retention index for three-membered ring), TNN5 (nitrogen atoms separated through 5 bond distance) and nitrogen counts, were identified as important structural features responsible for anticancer activity of MDA-MB-231 inhibitors. Five novel derivatives of glycyrrhetinic acid (GA) named GA-1, GA-2, GA-3, GA-4 and GA-5 were semi-synthesised and screened through the QSAR model. Further, in vitro activities of the derivatives were analysed against human TNBC cell line, MDA-MB-231. The result showed that GA-1 exhibits improved cytotoxic activity to that of parent compound (GA). Further, atomic property field (APF)-based 3D-QSAR and scoring recognise C-30 carboxylic group of GA-1 as major influential factor for its anticancer activity. The significance of C-30 carboxylic group in GA derivatives was also confirmed by molecular docking study against cancer target glyoxalase-I. Finally, the oral bioavailability and toxicity of GA-1 were assessed by computational ADMET studies. Communicated by Ramaswamy H. Sarma.
Derivatization, molecular docking and in vitro acetylcholinesterase inhibitory activity of glycyrrhizin as a selective anti-Alzheimer agent
Abdel Bar, Fatma M.,Elimam, Diaaeldin M.,Mira, Amira S.,El-Senduny, Fardous F.,Badria, Farid A.
supporting information, p. 2591 - 2599 (2018/04/20)
Acetylcholinesterase inhibitors (AChE-Is) increase both level and duration of action of acetylcholine (ACh); thus, alleviate symptoms of Alzheimer’s disease (AD). Glycyrrhizin, is the main active compound in liquorice root. Its aglycone, glycyrrhetinic acid, has shown several beneficial pharmacological activities. This study reports the synthesis and screening of a series of glycyrrhetinic acid analogs as AChE-Is. Fourteen derivatives were prepared, of which five derivatives are recorded as new viz., 3-phenyl-carbamoyl-18β-glycyrrhetinic acid (J9), 3-acetyl-18β-glycyrrhetinic-30-anilinamide (J10), 3-acetyl-18β-glycyrrhetinic-30-ethanolamide (J11), 3-acetyl-18β-glycyrrhetinic-30-n-butylamide (J12) and 18β-glycyrrhetinic acid-30-prenyl ester (J14), in addition to nine known derivatives (J1-J8 & J13). Compounds J12, J11, J0 and J3 showed remarkable AChE-I activity with IC50 values of 3.43, 5.39, 6.27 and 8.68?μM, respectively. These results are in full agreement with the docking study. The active compounds were non-cytotoxic to normal cells (WI-38).
Direct Carbon Isotope Exchange through Decarboxylative Carboxylation
Kingston, Cian,Wallace, Michael A.,Allentoff, Alban J.,Degruyter, Justine N.,Chen, Jason S.,Gong, Sharon X.,Bonacorsi, Samuel,Baran, Phil S.
supporting information, p. 774 - 779 (2019/01/14)
A two-step degradation-reconstruction approach to the carbon-14 radiolabeling of alkyl carboxylic acids is presented. Simple activation via redox-active ester formation was followed by nickel-mediated decarboxylative carboxylation to afford a range of complex compounds with ample isotopic incorporations for drug metabolism and pharmacokinetic studies. The practicality and operational simplicity of the protocol were demonstrated by its use in an industrial carbon-14 radiolabeling setting.
An efficient, scalable approach to hydrolyze flavonoid glucuronides via activation of glycoside bond
Jiang, Xue-Yang,Li, Xin-Chen,Liu, Wen-Yuan,Xu, Yun-Hui,Feng, Feng,Qu, Wei
, p. 1895 - 1903 (2017/03/11)
Hydrolyzing flavonoid glucuronides into corresponding aglycones posed some significant challenges. To improve acid-catalyzed hydrolysis process of flavonoid glucuronide, structures of glucuronide, hydrolysis parameters and post-processing were optimized. The optimized condition was performed by hydrolysis flavonoid glycoside methyl ester in a mixed solvent consisting of 2?mol/L H2SO4/EtOH/H2O (1/8/1, v/v/v) at 95?°C for 7?h and resulted in up to 90% aglycone yields, minimal byproduct formations and milder hydrolysis conditions. Furthermore, the optimized method avoids tedious purification steps and is easily conducted on a relatively large-scale using economical and commercially available reagents.
Synthesis and Biological Evaluation of Glycyrrhetic Acid Derivatives as Potential VEGFR2 Inhibitors
Yan, Tian-Long,Bai, Li-Fei,Zhu, Hai-Liang,Zhang, Wei-Ming,Lv, Peng-Cheng
, p. 1087 - 1096 (2017/07/11)
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 IC50 value of 1.08 μm. Compound 3 a also showed the most potent inhibitory activity against VEGFR2 tyrosine kinase, with an IC50 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.
