10226-29-6Relevant academic research and scientific papers
A galantamine–curcumin hybrid decreases the cytotoxicity of amyloid-beta peptide on SH-SY5Y cells
Mladenova, Kirilka,Stavrakov, Georgi,Philipova, Irena,Atanasova, Mariyana,Petrova, Svetla,Doumanov, Jordan,Doytchinova, Irini
, (2021)
Misfolded amyloid beta (Aβ) peptides aggregate and form neurotoxic oligomers. Membrane and mitochondrial damages, calcium dysregulation, oxidative stress, and fibril deposits are among the possible mechanisms of Aβ cytotoxicity. Galantamine (GAL) prevents apoptosis induced by Aβ mainly through the ability to stimulate allosterically the α7 nAChRs and to regulate the calcium cytosolic concentration. Here, we examined the cytoprotective effects of two GAL derivatives, namely compounds 4b and 8, against Aβ cytotoxicity on the human neuroblastoma cell line SH- SY5Y. The protective effects were tested at simultaneous administration, pre-incubation and postincubation, with Aβ. GAL and curcumin (CU) were used in the study as reference compounds. It was found that 4b protects cells in a similar mode as GAL, while compound 8 and CU potentiate the toxic effects of Aβ. Allosteric stimulation of α7 nAChRs is suggested as a possible mechanism of the cytoprotectivity of 4b. These and previous findings characterize 4b as a prospective non-toxic multi-target agent against neurodegenerative disorders with inhibitory activity on acetylcholinesterase, antioxidant, and cytoprotective properties.
A novel galantamine-curcumin hybrid as a potential multi-target agent against neurodegenerative disorders
Atanasova, Mariyana,Doytchinova, Irini,Philipova, Irena,Simeonova, Rumyana,Stavrakov, Georgi,Valkova, Iva,Zheleva, Dimitrina
, (2021)
The acetylcholinesterase (AChE) inhibitors are the main drugs for symptomatic treatment of neurodegenerative disorders like Alzheimer’s disease. A recently designed, synthesized and tested hybrid compound between the AChE inhibitor galantamine (GAL) and the antioxidant polyphenol curcumin (CU) showed high AChE inhibition in vitro. Here, we describe tests for acute and shortterm toxicity in mice as well as antioxidant tests on brain homogenates measured the levels of malondialdehide (MDA) and glutathione (GSH) and in vitro DPPH, ABTS, FRAP and LPO inhibition assays. Hematological and serum biochemical analyses were also performed. In the acute toxicity tests, the novel AChE inhibitor given orally in mice showed LD50 of 49 mg/kg. The short-term administration of 2.5 and 5 mg/kg did not show toxicity. In the ex vivo tests, the GAL-CU hybrid performed better than GAL and CU themselves; in a dose of 5 mg/kg, it demonstrates 25% reduction in AChE activity, as well as a 28% and 73% increase in the levels of MDA and GSH, respectively. No significant changes in blood biochemical data were observed. The antioxidant activity of 4b measured ex vivo was proven in the in vitro tests. In the ABTS assay, 4b showed radical scavenging activity 10 times higher than the positive control butylhydroxy toluol (BHT). The GAL-CU hybrid is a novel non-toxic AChE inhibitor with high antioxidant activity which makes it a prospective multitarget drug candidate for treatment of neurodegenerative disorders.
Oxidation of 1-alkylcycloalkanols with PbIV and MnIII compounds under mechanical activation
Kapustina,Sokova,Makhaev,Petrova,Nikishin
, p. 2080 - 2082 (1999)
A mechanoactivated solid-state oxidative decyclization of 1-alkylcycloalkanols under the action of the Pb(OAc)4-MX or Mn(OAc)3-MX systems (MX is a metal halide) was carried out for the first time. The reaction affords exclusively ω-haloalkanones.
Galantamine-curcumin hybrids as dual-site binding acetylcholinesterase inhibitors
Atanasova, Mariyana,Atanasova, Teodora,Doytchinova, Irini,Ivanov, Stefan,Konstantinov, Spiro,Lukarski, Atanas,Philipova, Irena,Stavrakov, Georgi,Zheleva, Dimitrina,Zhivkova, Zvetanka D.
, (2020/08/06)
Galantamine (GAL) and curcumin (CU) are alkaloids used to improve symptomatically neurodegenerative conditions like Alzheimer's disease (AD). GAL acts mainly as an inhibitor of the enzyme acetylcholinesterase (AChE). CU binds to amyloid-beta (Aβ) oligomers and inhibits the formation of Aβ plaques. Here, we combine GAL core with CU fragments and design a combinatorial library of GAL-CU hybrids as dual-site binding AChE inhibitors. The designed hybrids are screened for optimal ADME properties and BBB permeability and docked on AChE. The 14 best performing compounds are synthesized and tested in vitro for neurotoxicity and anti-AChE activity. Five of them are less toxic than GAL and CU and show activities between 41 and 186 times higher than GAL.
Ring-opening iodination and bromination of unstrained cycloalkanols through ?-scission of alkoxy radicals
Shi, Jiang-Ling,Wang, Yuankai,Wang, Zixuan,Dou, Bowen,Wang, Jianbo
supporting information, p. 5002 - 5005 (2020/05/18)
Ring-opening iodination or bromination of unstrained cycloalkanols with NaI or NaBr and PhI(OAc)2 under visible light irradiation is developed. In this protocol the concentration of I2is modulated through the generation of triiodide (I3-), thus significantly avoiding undesired side reactions. The reaction is under mild conditions and has a wide substrate scope, thus providing a practically useful method for accessing ω-iodo or ω-bromoketones.
Nitrogen-containing five-membered heteroaromatic compound and preparation method and application thereof
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Paragraph 0197; 0403; 0404; 0405, (2019/04/13)
The invention discloses a nitrogen-containing five-membered heteroaromatic compound as shown in structural formulae (I) and (II), a medicinal derivative, a hydrate, a composition containing the nitrogen-containing five-membered heteroaromatic compound and a preparation method thereof. The invention also disclose an application of the compound as a drug and as a cannabinoid acceptor adjustor for preventing and treating ache, inflammation, immune diseases and central nervous system diseases and the like.
INHIBITORS OF (ALPHA-V)(BETA-6) INTEGRIN
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Page/Page column 0289; 0290, (2018/09/16)
Disclosed are small molecule inhibitors of αvβ6 integrin, and methods of using them to treat a number of diseases and conditions.
Industrial production method of 3,3'-difluorobiphenyl
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Paragraph 0067; 0068; 0069; 0070, (2017/03/25)
The invention relates to a novel, safe, economical and environment-friendly production method of a useful chemical 3,3'-difluorobiphenyl. High-purity 3,3'-difluorobiphenyl can be prepared and obtained in a high-yield manner by making 3-fluorophenyl halogenated magnesium react with 1,2-dihalogenethane under the catalytic action of a trivalent ferric salt, and then treating a product by using an alkali or an acid. In addition, the method comprises a step of using and recycling an ethylene gas released in the reaction to prepare the initial raw material 1,2-dihalogenethane of the reaction, wherein the ethylene gas is a potential air pollutant.
AMINOPYRAZOLE DERIVATIVES
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Page/Page column 34, (2011/02/26)
The invention relates to aminopyrazole derivatives of formula (I), wherein A, E, R1 and R2 are as defined in the description, their preparation and their use as pharmaceutically active compounds.
An efficient and convenient protocol for highly regioselective cleavage of terminal epoxides to β-Halohydrins
Wang, Tao,Ji, Wen-Hao,Xu, Zhong-Yu,Zeng, Bu-Bing
experimental part, p. 1511 - 1513 (2009/10/23)
An efficient and facile strategy for the cleavage of terminal epoxides to β-halohydrins using active magnesium halides is described. The conversion proceeds smoothly at room temperature with high regioselectivity and good yields even when sensitive functional groups are present. Georg Thieme Verlag Stuttgart.
