13745-20-5Relevant academic research and scientific papers
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.
Isoliquiritigenin isolated from the roots of Glycyrrhiza uralensis inhibits LPS-induced iNOS and COX-2 expression via the attenuation of NF-κB in RAW 264.7 macrophages
Kim, Ji-Yeon,Park, Seung Jae,Yun, Kyung-Jin,Cho, Young-Wuk,Park, Hee-Juhn,Lee, Kyung-Tae
, p. 175 - 184 (2008)
In this study, the anti-inflammatory effects of flavonoids isolated from the roots of Glycyrrhiza uralensis (Leguminosae), namely, isoliquiritin (the glycoside of isoliquirigenin) and isoliquiritigenin (the aglycone of isoliquiritin) were evaluated on lipopolysaccharide (LPS)-treated RAW 264.7 macrophages. Isoliquiritigenin (ILG) more potently inhibited LPS-induced nitric oxide (NO) and prostaglandin E2 (PGE2) production than isoliquiritin (ILT). Consistent with these findings, ILG reduced the LPS-induced expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) at the protein and mRNA levels in a concentration-dependent manner, as determined by Western blotting and RT-PCR, respectively. In addition, the release of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), and the mRNA expression levels of these cytokines were reduced by ILG in a dose-dependent manner. Moreover, ILG attenuated the LPS-induced DNA binding activity and the transcription activity of nuclear factor-kappa B (NF-κB), and this was associated with a decrease in inhibitory kappa B-α (IκB-α) phosphorylation and in the subsequent blocking of p65 and p50 protein translocations to the nucleus. Furthermore, ILG suppressed the phosphorylations of IκB kinase (IKK), ERK1/2, and p38, whereas the phosphorylation of JNK1/2 was unaffected. These results suggest that the anti-inflammatory properties of ILG are caused by iNOS, COX-2, TNF-α, and IL-6 down-regulation due to NF-κB inhibition via the suppression of IKK, ERK1/2 and p38 phosphorylation in RAW 264.7 cells.
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.
Rotenoids, isoflavones and chalcones from the stem bark of Millettia usaramensis subspecies usaramensis
Yenesew, Abiy,Midiwo, Jacob O.,Waterman, Peter G.
, p. 295 - 300 (1998)
From the stem bark of Millettia usaramensis subsp. usaramensis four new 12a-hydroxyrotenoids with the unusual trans B/C ring junction ((+)-12a-epimillettosin, (+)-usararotenoid-A, (+)-12-dihydrousararotenoid-A, and (+)-usararotenoid-B), a new α-hydroxydihydrochalcone (α,4,2'-trihydroxy-4'-O-geranyldihydrochalcone), a new isoflavone, (norisojamicin), and a new cinnamyl alcohol derivative (4-O-geranylcinnamyl acetate) have been isolated and characterized. In addition, the known compounds 4'-O-geranylisoliquiritigenin, isoliquiritigenin, barbigerone, jamaicin and maximaisoflavone-G were identified. The structures were determined on the basis of spectroscopic evidence and chemical transformations.
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.
Isoliquiritigenin Derivatives Inhibit RANKL-Induced Osteoclastogenesis by Regulating p38 and NF-κB Activation in RAW 264.7 Cells
Choi, Jung-Won,Hwang, Ki-Chul,Jeong, Seongtae,Kim, Kundo,Kim, Sang Woo,Lee, Jiyun,Lee, Seahyoung,Lee, Yunmi,Lim, Soyeon,Oh, Sena
supporting information, (2020/09/17)
Bone diseases may not be imminently life-threatening or a leading cause of death such as heart diseases or cancers. However, as aging population grows in almost every part of the world, they surely impose significant socioeconomic burden on the society, not to mention the patients and their families. Osteoporosis is the most common type of bone disease, which frequently develops in seniors, especially in postmenopausal women. Although currently several anti-osteoclastic drugs designed to suppress excessive osteoclast activation, a major cause of osteoporosis, are commercially available, accompanying adverse effects ranging from mild to severe have been reported as well. Natural products have become increasingly popular because of their effectiveness with fewer side effects. Isoliquiritigenin (ILG), a natural flavonoid from licorice, has been reported to suppress osteoclast differentiation and activation. In the present study, newly synthesized ILG derivatives were screened for their anti-osteoporotic activity as more potent substitute candidates to ILG. Out of the 12 ILG derivatives tested, two compounds demonstrated significantly improved bone loss in vitro by inhibiting both osteoclastogenesis and osteoclast activity. The results of the present study indicate that these compounds may serve as a potential drug for osteoporosis and warrant further studies to evaluate their in vivo efficacy.
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.
Synthesis and evaluation of butein derivatives for in vitro and in vivo inflammatory response suppression in lymphedema
Kang, Hee,Ku, Jin-Mo,Lee, Jung-hun,Lee, Sukchan,Park, Kye Won,Roh, Kangsan,Song, Youngju
, (2020/05/01)
Herein, we demonstrate that butein (1) can prevent swelling in a murine lymphedema model by suppressing tumor necrosis factor α (TNF-α) production. Butein derivatives were synthesized and evaluated to identify compounds with in vitro anti-inflammatory activity. Among them, 20 μM of compounds 7j, 7m, and 14a showed 50percent suppression of TNF-α production in mouse peritoneal macrophages after lipopolysaccharide stimulation. Compound 14a, exhibited the strongest potency with an in vitro IC50 of 14.6 μM and suppressed limb volume by 70percent in a murine lymphedema model. The prodrug strategy enabled a six-fold increase in kinetic solubility of compound 1 and five-fold higher levels of active metabolite in the blood for compound 14a via oral administration in the pharmacokinetics study. We suggest that the compound 14a could be developed as a potential therapeutic agent targeting anti-inflammatory activity to alleviate lymphedema progression.
