10379-73-4Relevant articles and documents
Novel unsaturated glycyrrhetic acids derivatives: Design, synthesis and anti-inflammatory activity
Li, Bo,Cai, Shi,Yang, Yong-An,Chen, Shi-Chao,Chen, Rui,Shi, Jing-Bo,Liu, Xin-Hua,Tang, Wen-Jian
, p. 337 - 348 (2017)
To develop novel anti-inflammatory agents, a series of unsaturated glycyrrhetic acids were designed, synthesized and evaluated for anti-inflammatory activity using RAW264.7 cells. The structure-activity relationship (SAR) of NO inhibitory activity was analyzed. α,β-Unsaturated glycyrrhetic acids showed better activity, among them, compounds 6k and 6l with piperazine unit exhibited the most potent nitric oxide (NO) and interleukin-6 (IL-6) inhibitory activity (IC50 = 13.3 and 15.5 μM respectively). Furthermore, compound 6k could also significantly suppress LPS-induced iNOS and COX-2 expression and IL-6 production through MAPKs and NF-kB signaling pathway.
Conjugates of 18β-glycyrrhetinic acid derivatives with 3-(1H-benzo[d]imidazol-2-yl)propanoic acid as Pin1 inhibitors displaying anti-prostate cancer ability
Li, Kun,Ma, Tianyi,Cai, Jingjing,Huang, Min,Guo, Hongye,Zhou, Di,Luan, Shenglin,Yang, Jinyu,Liu, Dan,Jing, Yongkui,Zhao, Linxiang
, p. 5441 - 5451 (2017)
Twenty-six conjugates of 18β-glycyrrhetinic acid derivatives with 3-(1H-benzo[d]imidazol-2-yl)propanoic acid were designed and synthesized as Pin1 inhibitors. Most of these semi-synthetic compounds showed improved Pin1 inhibitory activity and anti-proliferative effects against prostate cancer cells as compared to 3-(1H-benzo[d]imidazol-2-yl)propanoic acid and GA. Compounds 10a and 12i were the most potent to inhibit growth of prostate cancer PC-3 with GI50 values of 7.80 μM and 3.52 μM, respectively. The enzyme inhibition ratio of nine compounds at 10 μM was over 90%. Structure-activity relationships indicated that both appropriate structure at ring C of GA and suitable length of linker between GA skeleton and benzimidazole moiety had significant impact on improving activity. Western blot assay revealed that 10a decreased the level of cell cycle regulating protein cyclin D1. Thus, these compounds might represent a novel anti-proliferative agent working through Pin1 inhibition.
Long circulating anionic liposomes for hepatic targeted delivery of cisplatin
Zhang, Liujie,Kuang, Ying,Liu, Jia,Liu, Zhilan,Huang, Shiwen,Zhuo, Renxi
, p. 76905 - 76914 (2016)
In this paper, a receptor-mediated liposomal drug delivery system (DDS) was developed aiming to deliver cisplatin (cis-diaminedichloroplatinum(ii); CDDP) targeting the liver. Acetyl glycyrrhetinic acid (AGA) was chosen as the hepatic targeting ligand and acetyl glycyrrhetinic acid-poly(ethylene glycol)-stearate (AGA-PEG-ST) was synthesized. Anionic 5-cholestene-3-beta-ol-3-hemisuccinate (CHO-HS) was also synthesized. The liposomal CDDPs were prepared by employing these functional moieties with phosphatidylcholine (PC) at various ratios. Meanwhile, methoxypolyethylene glycol-stearate (MPEG-ST) with an analogous structure but without AGA was also prepared as a control. The particle sizes of AGA modified liposomes ranged from 120 nm to 180 nm and the zeta potentials were located between -39.7 mV and -3.18 mV. The liposomes had encapsulation percentages of 51.5-61.7% and a loading capacity of 23.2-26.7% for CDDP. The transmission electron microscopy (TEM) observations showed that the liposomes had spherical morphologies with homogeneous distribution. In vitro cytotoxicity of CDDP-loaded liposomes against HepG2 human liver cancer cells and A549 human lung epithelial carcinoma cells were evaluated by MTT assays. The results demonstrated that the introduction of AGA could enhance the cytotoxicity of liposomal CDDP against HepG2 cells but showed less significant impact on A549 cells. CLSM observation and FCM measurement further confirmed that AGA modified liposomes had a stronger affinity to HepG2 cells than that of liposomes without AGA. The tissue distribution of calcein in mice indicated that AGA modified liposomes resulted in higher accumulation in the liver than that of liposomes without the AGA ligand. These results demonstrated the promise of AGA decorated anionic liposomes for hepatic targeted delivery of cisplatin.
Fluorofunctionalization of C=C Bonds with Selectfluor: Synthesis of β-Fluoropiperazines through a Substrate-Guided Reactivity Switch
Capilato, Joseph N.,Bume, Desta Doro,Lee, Wei Hao,Hoffenberg, Louis E. S.,Jokhai, Rayyan Trebonias,Lectka, Thomas
, p. 14234 - 14244 (2018)
The halofunctionalization of alkene substrates remains an essential tool for synthetic chemists. Herein, we report regioselective ammoniofluorination of unactivated alkenes through photochemical means. A one-pot transformation of the ammonium fluoride products into pharmaceutically relevant β-fluoropiperazines is highlighted. Furthermore, a substrate-guided reactivity switch is observed: certain alkenes are shown to react with the same fluorinating reagent to instead give the less-substituted fluoride. We hope that the ammoniofluorination reaction will be of utility in the area of medicinal chemistry, where nitrogen and fluorine are among the most important heteroatoms.
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Voss,Klein,Sauer
, p. 131 (1937)
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Synthesis and self-assembly properties of a glycyrrhetinic acid conjugate containing uracil and 2,6-diaminopyridine units
Hu, Jun,Lu, Jinrong,Li, Ruofan,Ju, Yong
, p. 891 - 894 (2011)
A novel glycyrrhetinic acid conjugate containing uracil and 2,6-diaminopyridine units was synthesized and the exclusive supramolecular dimeric structure through six intermolecular hydrogen bonds was characterized by NMR spectroscopy and ESI-MS. The supramolecular dimeric structure could recognize the polar molecule in aprotic polar solvents.
Synthesis and biological evaluation of novel curcuminoid derivatives
Cao, Ya-Kun,Li, Hui-Jing,Song, Zhi-Fang,Li, Yang,Huai, Qi-Yong
, p. 16349 - 16372 (2014)
Curcuminoids have been reported to possess multiple bioactivities, such as antioxidant, anticancer and anti-inflammatory properties. Three novel series of curcuminoid derivatives (11a-h, 15a-h and 19a-d) with enhanced bioactivity have been synthesized. Among the synthesized compounds, 11b exhibited the most significant activity with an MIC of 0.5 μ M /mL against selected medically important Gram-positive cocci (S aureus and S viridans) and Gram-negative bacilli (E. coli and E. cloacae). The derivatives exhibited remarkable results in an antioxidant test with an IC50 2.4- to 9.3-folder smaller than curcuminoids. With respect to antiproliferative activity against Hep-G2, LX-2, SMMC7221 and MDA-MB-231, the derivatives exhibited an effect stronger than curcuminoids with an IC50 ranging from 0.18 to 4.25 μ M.
Design and synthesis of novel glycyrrhetin ureas as anti-inflammatory agents for the treatment of acute kidney injury
Wang, Hongbo,Zuo, Jiawei,Zha, Liang,Jiang, Xia,Wu, Caixia,Yang, Yong-An,Tang, Wenjian,Shi, Tianlu
, (2021)
To develop new anti-inflammatory drugs for the prevention and treatment of acute kidney injury, a series of novel glycyrrhetic ureas were designed, synthesized and evaluated for anti-inflammatory activity using RAW264.7 cells. Compounds 5r-5u (2.04, 2.50, 3.25 and 2.48 μM, respectively) with acidic or neutral amino acid showed potent anti-inflammatory activity (IC50 = 2–3 μM for NO inhibition), amongst them, compound 5r also inhibited tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in a dose-dependent manner. In cisplatin-induced AKI mice model, compound 5r significantly reduced the level of pro-inflammatory factors, ameliorated the pathological damage of kidney tissue, and maintained the normal metabolic capacity.
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.
C3 and C20 diesterified glycyrrhetinic acid derivative, and preparation method and application thereof
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Paragraph 0070-0072; 0091, (2020/02/29)
The invention provides a C3 and C20 diesterified glycyrrhetinic acid derivative having a structure represented by formula I shown in the description, or a pharmaceutically acceptable salt, a solvate,an optical isomer or a polymorph thereof. Experimental results show that the C3 and C20 diesterified glycyrrhetinic acid derivative has a very good bacteriostatic effect on Staphylococcus aureus, caninhibit Staphylococcus aureus ATCC 6538, Staphylococcus aureus ATCC 12228 and Staphylococcus aureus ATCC 29213, and provides a new choice for anti-infective drugs for Staphylococcus aureus.
