13745-20-5Relevant articles and documents
Organolithium mediated synthesis of prenylchalcones as potential inhibitors of chemoresistance
Daskiewicz, Jean B.,Comte, Gilles,Barron, Denis,Di Pietro, Attilio,Thomasson, Francois
, p. 7095 - 7098 (1999)
A number of substituted chalcones have been prepped by a novel LiHMDS- mediated aldol condensation, the first method consistent with the use of alkali-labile protecting groups such as tert-butyldiphenylsilyl or tert- butyldimethylsilyl. Chalcone substitution by prenylation increases their binding affinity to P-glycoprotein responsible for cancer cells chemoresistance.
Total Synthesis of Xanthoangelol B and Its Various Fragments: Toward Inhibition of Virulence Factor Production of Staphylococcus aureus
Mizar, Pushpak,Arya, Rekha,Kim, Truc,Cha, Soyoung,Ryu, Kyoung-Seok,Yeo, Won-Sik,Bae, Taeok,Kim, Dae Wook,Park, Ki Hun,Kim, Kyeong Kyu,Lee, Seung Seo
, p. 10473 - 10487 (2018)
As an alternative strategy to fight antibiotic resistance, two-component systems (TCSs) have emerged as novel targets. Among TCSs, master virulence regulators that control the expression of multiple virulence factors are considered as excellent antivirulence targets. In Staphylococcus aureus, virulence factor expression is tightly regulated by a few master regulators, including the SaeRS TCS. In this study, we used a SaeRS GFP-reporter system to screen natural compound inhibitors of SaeRS, and identified xanthoangelol B 1, a prenylated chalcone from Angelica keiskei as a hit. We have synthesized 1 and its derivative PM-56 and shown that 1 and PM-56 both had excellent inhibitory potency against the SaeRS TCS, as demonstrated by various in vitro and in vivo experiments. As a mode of action, 1 and PM-56 were shown to bind directly to SaeS and inhibit its histidine kinase activity, which suggests a possibility of a broad spectrum inhibitor of histidine kinases.
Antiobesity and lipid lowering effects of Glycyrrhiza chalcones: Experimental and computational studies
Birari, Rahul B.,Gupta, Shikhar,Mohan, C. Gopi,Bhutani, Kamlesh K.
, p. 795 - 801 (2011)
Twelve flavonoids (1-12), isolated from Glycyrrhiza glabra roots were evaluated for their pancreatic lipase (PL) inhibitory activity in vitro. The structures of the isolated compounds were elucidated by spectroscopic methods. Amongst all the compounds 7, 8, 10 and 11 showed strong inhibition against PL with IC50 values of 7.3 μM, 35.5 μM, 14.9 μM and 37.6 μM, respectively. Molecular docking studies on the most active compound 7 revealed that it binds with the key amino acid residues of the PL active site. In silico absorption, distribution, metabolism and excretion (ADME) parameters were also computed on the active compounds to determine their preliminary pharmacokinetic properties. Further, investigations were carried out to determine the antiobesity and lipid lowering effects of 7 and 10 in high fat diet (HFD) fed male SD rats. In the rats supplemented with compound 7 the body weight increase was only 23.2 ± 3.6 g as compared to 64.2 ± 0.5 g in the HFD control group while in the rats treated with compound 10 showed 23.2 ± 3.6 g weight gain only. Compound 7 decreased the levels of plasma total cholesterol (TC) to 84.6 ± 1.4 mg/dl and plasma total triglycerides (TG) to 128.8 ± 6.0 mg/dl. Compound 10 also lowered the plasma TC and TG levels considerably. The results indicate the potential of the chalcone scaffold as a source of PL inhibitors for preventing obesity.
Neolicuroside - a New Chalcone Glycoside from the Roots of Glycyrrhiza glabra
Miething, Holger,Speicher-Brinker, Annette
, p. 141 - 143 (1989)
Licuroside (1), first isolated by Litvinenko from the roots of Glycyrrhiza glabra, is not a homogeneous compound.It is separated into two isomeric glycosides 1 and 2 using modern chromatographic techniques (HPLC, LPLC).The structure of 2 is confirmed as isoliquiritigenin-4-β-D-apiofuranosyl-2''-β-D-glucopyranoside.So far 2 has not been described.The name neolicuroside is proposed.The structure of 1 is established as isoliquirtigenin-4'-β-D-apiofuranosyl-2''-β-D-glucopyranoside by spectroscopic methods.
Discovery of isoliquiritigenin analogues that reverse acute hepatitis by inhibiting macrophage polarization
Yang, Junjie,Hu, Fanjie,Guo, Chengjun,Liang, Yuqing,Song, Haiying,Cheng, Kui
, (2021/06/15)
Screening a natural product library of 850 compounds yield isoliquiritigenin as an effective anti-inflammatory agent by inhibiting the production of pro-inflammatory NO induced by Pam3CSK4, while its activity accompanied by toxicity. Further studies obtained the optimized isoliquiritigenin derivative SMU-B14, which can inhibit Pam3CSK4 triggered toll-like receptor 2 (TLR2) signaling with low toxicity and high potency. Preliminary mechanism studies indicated that SMU-B14 worked through TLR2/MyD88, phosphorylation of IKKα/β, leading to the reduce degradation of NF-κB related IKBα and p65 complex, then inhibited the production of inflammatory cytokines, such as TNF-α, IL-6, IL-1β both in human and murine cell lines. Subsequent polarization experiments showed SMU-B14 significant reversed the polarization of M1 phenotype primary macrophage activated by Pam3CSK4 in vitro, and reduced the infiltration of neutrophil and polarization of M1-type macrophage, decreased serum alanine transaminase (ALT), as a result protected liver from being injured in vivo. In summary, we obtained an optimized lead compound SMU-B14 and found it functionally blocked TLR2/MyD88/NF-κB signaling pathway to down-regulate the production of inflammatory cytokines resulted significant liver protection property.
Synthesis and biological evaluation of isoliquiritigenin derivatives as a neuroprotective agent against glutamate mediated neurotoxicity in HT22 cells
Selvaraj, Baskar,Kim, Dae Won,Huh, Gyuwon,Lee, Heesu,Kang, Kyungsu,Lee, Jae Wook
, (2020/03/05)
Glutamate-induced neurotoxicity is characterized by cellular Ca2+ uptake, which is upstream of reactive oxygen species (ROS)-induced apoptosis signaling and MAPKs activation. In the present study, we synthesized isoliquiritigenin analogs with electron-donating and electron-withdrawing functional groups. These analogs were evaluated for neuroprotective effect against glutamate-induced neurotoxicity in HT22 cells. Among these analogs, compound BS11 was selected as a potent neuroprotective agent. Cellular Ca2+ concentration, ROS level, MAPKs activation and AIF translocation to the nucleus were increased upon treatment with 5 mM glutamate. In contrast, we identified that compound BS11 reduced the cellular Ca2+ concentration and ROS level upon glutamate exposure. Western blot analysis showed that MAPK activation was decreased by treatment with compound BS11. We further identified that cotreatment of compound BS11 and glutamate inhibited translocation of AIF to the nucleus.
Natural product-based design, synthesis and biological evaluation of 2′,3,4,4′-tetrahydrochalcone analogues as antivitiligo agents
Zhong, Hui,Zhou, Jia,An, Xiao-Hong,Hua, Ying-Rong,Lai, Yi-Fan,Zhang, Rui,Ahmad, Owais,Zhang, Ye,Shang, Jing
, p. 523 - 533 (2019/04/01)
A bioactive component, 2′,3,4,4′-tetrahydrochalcone (RY3-a) was first isolated from Vernohia anthelmintica (L.) willd seeds, and a set of its analogs, RY3-a-1–RY3-a-15 and RY3-c were designed and synthesized. Biological activity assays showed that RY3-c exhibited better melanogenesis and antioxidant activity and lower toxicity in comparison with RY3-a and butin. Further study tests showed that RY3-c exhibited better melanogenesis activity compared with the positive control 8-methoxypsoralan (8-MOP) in a vitiligo mouse model, suggesting that RY3-c is a good candidate antivitiligo agent. Mechanistic studies showed that RY3-c could repair cell damage induced by excessive oxidative stress and may exert melanin synthesis activity in the mouse melanoma B16F10 cell line by activating the mitogen-activated protein kinase (MAPK) pathway and the upregulation of c-kit.
