118525-40-9Relevant articles and documents
Synthesis of icariin from kaempferol through regioselective methylation and para-Claisen - Cope rearrangement
Mei, Qinggang,Wang, Chun,Zhao, Zhigang,Yuan, Weicheng,Zhang, Guolin
, p. 1220 - 1225 (2015)
The hemisynthesis of the naturally occurring bioactive flavonoid glycoside icariin (1) has been accomplished in eleven steps with 7% overall yield from kaempferol. The 4?-OH methylation of kaempferol, the 8-prenylation of 3-O-methoxymethyl-4?-O-methyl-5- O-prenyl-7-O-benzylkaempferol (8) via para-Claisen-Cope rearrangement catalyzed by Eu(fod)3 in the presence of NaHCO3 , and the glycosylation of icaritin (3) are the key steps.
A novel anticancer agent, icaritin, induced cell growth inhibition, G1 arrest and mitochondrial transmembrane potential drop in human prostate carcinoma PC-3 cells
Huang, Xin,Zhu, Danyan,Lou, Yijia
, p. 26 - 36 (2007)
Icariin and icaritin with prenyl group have been demonstrated for their selective estrogen receptor modulating activities. We screened their effects on cell growth in human prostate carcinoma PC-3 cell line (estrogen receptor positive) in vitro. PC-3 cell line was used for the measurement of anti-carcinoma activities of 0-100 μmol/l icaritin and 30 μmol/l icariin. 1 μmol/l 17-β estradiol (E2) served as the estrogen positive control, and 1 μmol/l ICI 182,780 [7 α-[9 (4,4,5,5,5-pentafluoropentyl) sulfinyl] nonyl]-estra-1,3,5(10)-triene-3,17h-diol]] served as the specific estrogen receptor antagonist. Primary cultured rat prostate basal cells used as cell growth selective control. The growth-inhibitory effects were analyzed using MTT assay, and fluorochrome staining, flow cytometry, and immunoblotting were employed to illustrate the possible mechanisms. When treated with icaritin for 24 to 72 h, cell growth was strongly inhibited (at 48 h IC50 was 10.74 ± 1.59 μmol/l, P 50 could be observed when co-incubated with ICI 182,780. Icaritin-induced growth inhibition was associated with G1 arrest (P 2-M arrest depending upon doses. Consistently with G1 arrest, icaritin increased protein expressions of pRb, p27Kip1 and p16Ink4a, while showed decrease in phosphorylated pRb, Cyclin D1 and CDK4. Comparatively, icariin has much lower effects on PC-3 cells and showed only weak G1 arrest, suggesting a possible structure-activity relationship. These findings suggested a novel anticancer efficacy of icaritin mediated selectively via induction of cell cycle arrest but not associated with estrogen receptors in PC-3 cells.
Magnesium dicarboxylates promote the prenylation of phenolics that is extended to the total synthesis of icaritin
Fu, Xuewen,Lu, Xiaoxia,Wang, Chun,Wen, Yongju,Xiong, Wei,Zhang, Guolin,Zhang, Jichao
, p. 1117 - 1124 (2022/02/16)
The prenylation of phenolic substrates promoted by magnesium dicarboxylates was developed. An investigation of the scope demonstrated that substrates with electron-donating group(s) gave better yields than those with electron-withdrawing group(s). Althoug
Phosphate ester derivative of herba epimedii as well as preparation method and application of phosphate ester derivative
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Paragraph 0033-0038, (2021/06/26)
The invention belongs to the technical field of medicines, and discloses a phosphate ester derivative of herba epimedii as well as a preparation method and application of the phosphate ester derivative. The chemical structural formula of the phosphate ester derivative of the herba epimedii is represented by the formula (1), wherein R1 is selected from groups defined in the specification, or R2 is selected from H or R1, and R3 is selected from H or a group defined in the specification. According to the phosphate ester derivative of the herba epimedii, the cytotoxicity of the partially modified derivative is remarkably enhanced compared with that of an unmodified derivative, and meanwhile the phosphate ester derivative of the herba epimedii has the anti-osteoporosis effect. The phosphate ester derivative of the herba epimedii can be applied to the field of preparation of drugs for prostate cancer cells, anti-osteoporosis health-care products, pharmaceutical excipients or drugs.
Convenient and efficient total synthesis method for icaritin and derivatives of icaritin
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Paragraph 0063; 0084-0088, (2020/02/06)
The invention belongs to the field of natural medicine synthesis and particularly relates to a convenient and efficient total synthesis method for icaritin and derivatives of icaritin. The specific technical scheme is as follows: 2'-hydroxyacetophenone and benzaldehyde are used as raw materials, firstly, isopentene groups are introduced in aromatic rings of raw materials under the catalysis of anorganic polyacid metal ion complex, a flavonol framework is constructed under mild and green conditions, and an isopentenyl flavone compound comprising the icaritin and derivatives of icaritin is further synthesized. The method effectively overcomes the limitation of poor substrate solubility and poor regioselectivity when flavone is constructed firstly and then isopentene groups are introduced, the problems of frequent introduction and removal of protecting groups in a conventional isopentenylation method are solved, and the synthesis route is greatly simplified; and meanwhile, the problems of complex products and more byproducts in an isopentene group rearrangement method are solved. The total synthesis method provided by the invention is mild in condition, convenient to operate, high intotal yield and suitable for mass production of the isopentenyl flavone compound.
ANALOGS OF THE NATURAL PRODUCT ICARIIN
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Paragraph 00168; 00192, (2020/03/02)
Provided herein are analogs of the natural product icariin represented by Structural Formula (I) or a pharmaceutically acceptable salt thereof. The analogs can be used to modulate (e.g., inhibit, such as by competitive inhibition) PDE5 and thereby treat a wide range of PDE5- mediated diseases, including cardiovascular, gastrointestinal, pulmonary, musculoskeletal, neurological and reproductive diseases. Also provided herein are compositions and methods including compounds of Structural Formula (I).
Preparation and medical application methods of icaritin derivative
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, (2019/10/23)
The invention relates to preparation and medical application methods of an icaritin derivative. The preparation method comprises taking trihydroxyacetophenone, chloromethyl methyl ether and the like as initial raw materials to connect isopentene groups to an 8th carbon through vicinal rearrangement, then performing serial reaction of formation of a flavone framework, and lastly, performing dehydration to introduce propylene groups to synthesize the icaritin derivative. The preparation method of the icaritin derivative is low in the cost of the synthetic routes, simple in operation, high in recovery rate and applicable to industrial production. Pharmacological effect experiments prove that the icaritin derivative has the pharmacological effect of activating organism endogenous stem cells and achieves the rehabilitation function of repair traumatic pathological changes of blood vessels, nerves, endothelial cells and matrixes and can be applied to preparing drugs for repairing traumatic pathological changes of tissues, thereby having a good prospect in fields such as drugs for rehabilitation of pathological changes of erectile dysfunction.
Exploration of icariin analog structure space reveals key features driving potent inhibition of human phosphodiesterase-5
Chau, Yasmin,Li, Fu-Shuang,Levsh, Olesya,Weng, Jing-Ke
, (2019/09/30)
The natural product icariin inhibits human phosphodiesterase-5 (PDE5) and represents a unique pharmacophore for treating erectile dysfunction, pulmonary hypertension, and other diseases. In this study, we explore the available icariin-derived chemical scaffolds through medicinal chemistry to develop novel icariin PDE5 inhibitors with improved potency and specificity. We synthesized six novel semi-synthetic icariin analogs as well as three naturally occurring icariin analogs, and characterized the structure-activity relationship in the context of human PDE5 inhibition using in vitro enzyme inhibition and kinetics assays and molecular modeling. Mammalian-cell-based assays and in vitro enzyme inhibition assays against human PDE6C further helped to identify the most potent and selective icariin analogs. Our results reveal the synergistic contribution of functional groups at the C3 and C7 positions of the icariin backbone towards PDE5 inhibition. Whereas a hydrophobic and flexible alkanol group at the C7 position is sufficient to enhance icariin analog potency, combining this group with a hydrophilic sugar group at the C3 position leads to further enhancement of potency and promotes specificity towards PDE5 versus PDE6C. In particular, compounds 3 and 7 exhibit Ki values of 0.036 ± 0.005 μM and 0.036 ± 0.007 μM towards PDE5 respectively, which are approaching those of commercial PDE5 inhibitors, and can effectively reduce GMP levels in cultured human BJ-hTERT cells. This study identifies novel icariin analogs as potent and selective PDE5 inhibitors poised to become lead compounds for further pharmaceutical development.
Flavone derivative and preparation method and medical application of flavone derivative
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Paragraph 0084; 0093, (2019/09/05)
The invention relates to a flavone derivative and a preparation method and medical application of the flavone derivative. The flavone derivative is prepared through a mode that anhydroicaritin is taken as a mother nucleus, and group addition and reduction are conducted. It is proved through a pharmacological experiment that the flavone derivative has the pharmacological effect of activating endogenous stem cells in the body, achieves the effects of repairing injury-type pathological changes of blood vessel cells, nerve cells, endothelial cells and the matrix and recovering functions, can be used for preparing medicines for repairing the tissue-injury pathological changes and has a good prospect in preparing medicines for conducting rehabilitation treatment on erectile dysfunction pathological changes.
Icarisid I type compound, derivatives, pharmaceutical composition and application thereof
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, (2019/03/06)
The invention provides an icarisid I type compound and derivatives, or a stereisomer, geometrical isomer, tautomer, nitrogen oxide, hydrate, solvate, metabolite, pharmaceutically-acceptable salt or prodrug of the compound of formula I (shown in the specification). The synthetic materials of the icarisid I type compound and derivatives are selected from quercetin, apigenin, kaempferol, scutellarein, wild scutellarein, chrysin, daidzein, genistein, isorhamnetin, myricetin, luteolin, fisetin or icaritin. By methods of chemical synthesis and bioengineering, the icarisid I type compound and derivatives with better biological effect and higher economic benefit can be synthesized by flavone compounds (such as the apigenin and the quercetin and the like) with higher existence in nature.
