146236-29-5Relevant articles and documents
Bioactive microbial metabolites from glycyrrhetinic acid
Maatooq, Galal T.,Marzouk, Amani M.,Gray, Alexander I.,Rosazza, John P.
, p. 262 - 270 (2010)
Biotransformation of 18β-glycyrrhetinic acid, using Absidia pseudocylinderospora ATCC 24169, Gliocladium viride ATCC 10097 and Cunninghamella echinulata ATCC 8688a afforded seven metabolites, which were identified by different spectroscopic techniques (1H, 13C NMR, DEPT, 1H-1H COSY, HMBC and HMQC). Three of these metabolites, viz. 15α-hydroxy-18α-glycyrrhetinic acid, 13β-hydroxy-7α,27-oxy-12-dihydro-18β-glycyrrhetinic acid and 1α-hydroxy-18β-glycyrrhetinic acid are new. The 13C NMR data and full assignment for the known metabolite 7β, 15α-dihydroxy-18β-glycyrrhetinic acid are described here for the first time. The major metabolites were evaluated for their hepatoprotective activity using different in vitro and in vivo models. These included protection against FeCl3/ascorbic acid-induced lipid peroxidation of normal mice liver homogenate, induction of nitric oxide (NO) production in rat macrophages and in vivo hepatoprotection against CCl4-induced hepatotoxicity in albino mice.
Influence of honey on the gastrointestinal metabolism and disposition of glycyrrhizin and glycyrrhetic acid in rabbits.
Ching, Hui,Hou, Yu-Chi,Hsiu, Su-Lan,Tsai, Shang-Yuan,Chao, Pei-Dawn Lee
, p. 87 - 91 (2002)
To investigate the effects of honey on the pharmacokinetics of glycyrrhizin and glycyrrhetic acid, administration of glycyrrhizin or glycyrrhetic acid with and without honey was carried out in rabbits in a randomized crossover design. An in vitro study using rabbit fecal flora was employed to elucidate the mechanism of the interaction. HPLC methods were used for the determination of glycyrrhizin, glycyrrhetic acid and 3-dehydroglycyrrhetic acid concentrations in serum and feces. Paired and unpaired Student's t-tests were used for statistical comparisons for in vivo and in vitro studies, respectively. Our study indicated that the area under the curve (AUC0-t) of glycyrrhetic acid was significantly enhanced by 53% when honey was concomitantly given with glycyrrhizin, whereas that of glycyrrhizin was not significantly altered. Nevertheless, lack of effect was observed when honey was concurrently given with glycyrrhetic acid. Fecal study indicated that both the hydrolysis of glycyrrhizin to glycyrrhetic acid and subsequent oxidation of glycyrrhetic acid to 3-dehydroglycyrrhetic acid were significantly affected in the presence of honey to result in more glycyrrhetic acid available for absorption. It could be concluded that honey significantly affected the gastrointestinal metabolism of glycyrrhizin and resulted in the increased glycyrrhetic acid exposure. Therefore, honey might enhance the efficacy and adverse effects of glycyrrhizin.
Indole-and pyrazole-glycyrrhetinic acid derivatives as ptp1b inhibitors: Synthesis, in vitro and in silico studies
Cortés-Benítez, Francisco,De-La-cruz-martínez, Ledy,Duran-Becerra, Constanza,Espinosa-Chávez, Julio,Germán-Acacio, Juan Manuel,González-Andrade, Martin,Páez-Franco, José C.,Pérez-Villanueva, Jaime,Palacios-Espinosa, Juan Francisco,Soria-Arteche, Olivia,Torres-Valencia, J. Martin
, (2021)
Regulating insulin and leptin levels using a protein tyrosine phosphatase 1B (PTP1B) inhibitor is an attractive strategy to treat diabetes and obesity. Glycyrrhetinic acid (GA), a triter-penoid, may weakly inhibit this enzyme. Nonetheless, semisynthetic derivatives of GA have not been developed as PTP1B inhibitors to date. Herein we describe the synthesis and evaluation of two series of indole-and N-phenylpyrazole-GA derivatives (4a–f and 5a–f). We measured their inhibitory activity and enzyme kinetics against PTP1B using p-nitrophenylphosphate (pNPP) assay. GA derivatives bearing substituted indoles or N-phenylpyrazoles fused to their A-ring showed a 50% inhibitory concentration for PTP1B in a range from 2.5 to 10.1 μM. The trifluo-romethyl derivative of indole-GA (4f) exhibited non-competitive inhibition of PTP1B as well as higher potency (IC50 = 2.5 μM) than that of positive controls ursolic acid (IC50 = 5.6 μM), claramine (IC50 = 13.7 μM) and suramin (IC50 = 4.1 μM). Finally, docking and molecular dynamics simulations provided the theoretical basis for the favorable activity of the designed compounds.
Brieskorn,Eschelbach
, p. 752,759 (1979)
Synthesis and biological evaluation of pentacyclic triterpenoid derivatives as potential novel antibacterial agents
Wu, Panpan,Tu, Borong,Liang, Jinfeng,Guo, Shengzhu,Cao, Nana,Chen, Silin,Luo, Zhujun,Li, Jiahao,Zheng, Wende,Tang, Xiaowen,Li, Dongli,Xu, Xuetao,Liu, Wenfeng,Zheng, Xi,Sheng, Zhaojun,Roberts, Adam P.,Zhang, Kun,Hong, Weiqian David
, (2021)
A series of ursolic acid (UA), oleanolic acid (OA) and 18β-glycyrrhetinic acid (GA) derivatives were synthesized by introducing a range of substituted aromatic side-chains at the C-2 position after the hydroxyl group at C-3 position was oxidized. Their antibacterial activities were evaluated in vitro against a panel of four Staphylococcus spp. The results revealed that the introduction of aromatic side-chains at the C-2 position of GA led to the discovery of potent triterpenoid derivatives for inhibition of both drug sensitive and resistant S. aureus, while the other two series derivatives of UA and OA showed no significant antibacterial activity even at high concentrations. In particular, GA derivative 33 showed good potency against all four Staphylococcus spp. (MIC = 1.25–5 μmol/L) with acceptable pharmacokinetics properties and low cytotoxicity in vitro. Molecular docking was also performed using S. aureus DNA gyrase to rationalize the observed antibacterial activity. This series of GA derivatives has strong potential for the development of a new type of triterpenoid antibacterial agent.
A versatile tailoring tool for pentacyclic triterpenes of Penicillium griseofulvum CICC 40293
Zhu, Yuyuan,Shen, Pingping,Zhou, Xiaoyang,Fei, Yinuo,Wang, Wei,Raj, Richa,Du, Zhichao,Ge, Haixia,Wang, Weiwei,Xu, Shaohua,Yu, Boyang,Zhang, Jian
, p. 195 - 201 (2021/07/09)
In the biosynthetic pathway of pentacyclic triterpenes (PTs), tailoring reactions can produce a wide range of end products from a small number of common scaffolds and the microbial transformation has also been established as an alternative technique for this purpose. In this study, we explored the tailoring reactions involved in the microbial transformation of pentacyclic triterpenes by Penicillium griseofulvum CICC 40293. Preparative biotransformation of eight different PTs from three scaffolds resulted in the isolation of thirteen metabolites. The structures of metabolites were elucidated by HR-ESI-MS, 1D, and 2D NMR spectroscopy. We discovered the highly efficient regio- and stereo-selective hydroxylation of inactivated sp3 CH2 and CH3 on the position of 2α, 7β, 15α, 21β, 23(angular methyl), and 30?COOH glycosylation, this versatile tailoring system for PTs would provide an effective method for expanding their structural diversities. In addition, all compounds were subjected to the bioassay on the model of lipopolysaccharide (LPS)-stimulated RAW 264.7 cells to evaluate their anti-inflammatory activity through nitric oxide (NO) inhibition activity. Compounds 2a and 5a exhibited excellent NO inhibitory activity with IC50 values of 8.35 ± 2.81 μM and 19.60 ± 4.25 μM, respectively.
