703-29-7Relevant articles and documents
Inhibition of BACE1 and amyloid β aggregation by polyketide from Streptomyces sp.
Yokoya, Masashi,Nakai, Keiyo,Kawashima, Miki,Kurakado, Sanae,Sirimangkalakitti, Natchanun,Kino, Yoshihiro,Sugita, Takashi,Kimura, Shinya,Yamanaka, Masamichi,Saito, Naoki
, p. 264 - 276 (2021/11/30)
Alzheimer's disease (AD) causes cognitive impairment in the elderly and is a severe problem worldwide. One of the major reasons for the pathogenesis of AD is thought to be due to the accumulation of amyloid beta (Aβ) peptides that result in neuronal cell death in the brain. In this study, bioassay-guided fractionation was performed to develop seed compounds for anti-AD drugs that can act as dual inhibitors of BACE1 and Aβ aggregation from secondary metabolites produced by Streptomyces sp. To improve the solubility, the crude extracts were methylated with trimethylsilyl (TMS) diazomethane and then purified to yield polyketides 1–5, including the new compound 1. We synthesized the compounds 6 and 7 (original compounds 2 and 3, respectively), and their activities were evaluated. KS-619-1, the demethylated form of 4 and 5, was isolated and evaluated for its inhibitory activity. The IC50 values for BACE1 and Aβ aggregation were found to be 0.48 and 1.1?μM, respectively, indicating that KS-619-1 could be a lead compound for the development of therapeutic agents for AD.
Biomimetic synthesis and anti-inflammatory evaluation of violacin A analogues
Wu, Wenxi,Mu, Yu,Liu, Bo,Wang, Zixuan,Guan, Peipei,Han, Li,Jiang, Mingguo,Huang, Xueshi
, (2021/04/23)
Violacin A, a chromanone derivative, isolated from a fermentation broth of Streptomyces violaceoruber, has excellent anti-inflammatory potential. Herein, a biogenetically modeled approach to synthesize violacin A and twenty-five analogues was described, which involved the preparation of aromatic polyketide precursor through Claisen condensation and its spontaneous cyclization. The inhibitory effect on nitric oxide (NO) production of all synthetic molecules was evaluated by lipopolysaccharide (LPS)-induced Raw264.7 cells. The results revealed that introduction of aliphatic amine moieties on C-7 obviously improved the anti-inflammation effect of violacin A, and also the aromatic ether instead of ketone group at side chain was favorable to increase the activity. Among them, analogue 7a and 16d were screened as the most effective anti-inflammatory candidates. Molecular mechanism research revealed that 7a and 16d acquired anti-inflammatory ability due to the inhibition of NF-κB signaling pathway.
5-methyl chromone as well as preparation method and application thereof
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Paragraph 0061-0064, (2021/01/12)
The invention provides 5methyl chromone as well as a preparation method and application thereof. The 5methyl chromone has the following structure, wherein R1 and R2 are alkyl. The substituted chromonehas the biological activity of inhibiting tyrosinase. T
Synthesis method and application ofaloesone
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Paragraph 0041-0045, (2021/10/27)
The invention provides a synthesis method and application of aloesone. According to the method, a compound A, a hydrogen chloride solution and isopropanol are mixed, the molar ratio of the compound A to hydrogen chloride is 1:(4.0-4.5), the mixture is heated to 40-50 DEG C, stirring reaction is performed for 1-2 h, after the reaction, pressure reducing concentrating is performed to remove the solvent to obtain a concentrate, and the concentrate is purified by column chromatography to obtain a target product aloesone, wherein the structure of the compound A is shown as a formula (a). The synthesis method of the aloesonehas the advantages of low cost, easiness in synthesis, high yield and better industrial production.
Total synthesis and anti-inflammatory evaluation of violacin A and its analogues
Liu, Qingyin,Mu, Yu,An, Qi,Xun, Jiali,Ma, Jian,Wu, Wenxi,Xu, Minjuan,Xu, Jun,Han, Li,Huang, Xueshi
, (2019/11/26)
A concise total synthesis of an exceedingly potent anti-inflammatory agent violacin A as well as the preparation of thirty analogues of this lead from commercially available orcinol are described. Highlights of our synthetic efforts involve Friedel-Crafts acylation, the regioselective etherification and esterification of phenolic hydroxyl groups, and Baker-Venkatamaran rearrangement to form basic skeleton of violacin A. The deprotection reaction with Pd-catalytic was involved to avoid the elimination of the hemiacetal hydroxyl at C2. In addition, all synthetic compounds were screened for anti-inflammatory activity against nitric oxide (NO) production using lipopolysaccharide (LPS)-induced Raw264.7 cells. A range of violacin A derivatives 11b, 11d, 11f, 12e, 12g, 13g, 17d-g exhibited stronger anti-inflammatory effect than that of violacin A. Notably, halogeno-benzyloxy substituent at C-7 were favourable for anti-inflammatory activities of violacin A derivatives. Additionally, Western blot results indicated halogeno-benzyloxy derivatives inhibited pro-inflammatory cytokines releases correlated with the suppression of NF-κB signaling pathway.
First synthesis of rugosaflavonoid and its derivatives and their activity against breast cancer
Puranik, Ninad V.,Srivastava, Pratibha
, p. 33052 - 33060 (2017/07/07)
Rugosaflavonoid, is a secondary metabolite isolated from the plant Rosa rugosa was synthesized in five simple steps from commercially available 3,5-dihydroxy benzoic acid involving domino aldol-Michael-oxidation reaction. This is the first report of the synthesis of rugosaflavonoid (6a). A series of its derivatives were also synthesized, characterized and evaluated for the cytotoxicity against the breast cancer MCF-7 and normal NIH3T3 cell lines. The synthetic derivatives of rugosaflavonoid showed comparable activity in both the cell lines and compounds 6d, 6e and 6f, which were found to be cytotoxic towards MCF-7 cell lines but nontoxic to NIH3T3 cell lines at 5 μM concentration. In an attempt to explore the mode of action of the best active compounds, docking on the ATP binding site of EGFR (1M17) was performed considering that EGFR over-expressed in most of the tumors. The docking score (Gscore) of 6f and standard quercetin was found to be -8.608 and -8.310 respectively.
DIHYDROOROTIC ACID DEHYDROGENASE INHIBITOR
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Paragraph 0122; 0126; 0127, (2015/04/15)
The present invention provides a novel dihydroorotic acid dehydrogenase inhibitor which is applicable to various diseases. When used as an active ingredient, a compound represented by formula (I): (wherein X represents a halogen atom, R1 represents a hydrogen atom, R2 represents an alkyl group containing 1 to 7 carbon atoms, R3 represents -CHO, and R4 represents -CH2-CH=C(CH3)-R0 (wherein R0 represents an alkyl group containing 1 to 12 carbon atoms which may have a substituent on the terminal carbon and/or on a non-terminal carbon, etc.)), an optical isomer thereof or a pharmaceutically acceptable salt thereof has a high inhibitory effect on dihydroorotic acid dehydrogenase and can be used as an immunosuppressive agent, a therapeutic agent for rheumatism, an anticancer agent, a therapeutic agent for graft rejection, an antiviral agent, an anti-H. pylori agent, a therapeutic agent for diabetes or the like.
NOVEL DIHYDROXYBENZENE DERIVATIVES AND ANTIPROTOZOAL AGENT COMPRISING SAME AS ACTIVE INGREDIENT
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Paragraph 0133; 0137; 0138, (2013/09/26)
Novel compounds below are useful for preventing or treating diseases caused by protozoans. At least one of a compound represented by Formula (I) (wherein, X represents a hydrogen atom or a halogen atom; R1 represents a hydrogen atom; R2 represents a hydrogen atom or a C1-7 alkyl group; R3 represents -CHO, -C(=O)R5, -COOR5 (wherein R5 represents a C1-7 alkyl group), -CH2OH or -COOH; and R4 represents a C1-16 alkyl group having one or more substituents on a terminal carbon atom and/or non-terminal carbon atom(s), a C2-16 alkenyl group having one or more substituents on a terminal carbon atom and/or non-terminal carbon atom(s), or a C2-16 alkynyl group having one or more substituents on a terminal carbon atom and/or non-terminal carbon atom(s)), an optical isomer thereof, and a pharmaceutically acceptable salt is used.
Anti-AIDS agents 79. Design, synthesis, molecular modeling and structure-activity relationships of novel dicamphanoyl-2′,2′- dimethyldihydropyranochromone (DCP) analogs as potent anti-HIV agents
Zhou, Ting,Shi, Qian,Chen, Chin-Ho,Zhu, Hao,Huang, Li,Ho, Phong,Lee, Kuo-Hsiung
experimental part, p. 6678 - 6689 (2010/10/18)
In a continued study, 23 3′R,4′R-di-O-(-)-camphanoyl-2′, 2′-dimethyldihydropyrano[2,3-f]chromone (DCP) derivatives (5-27) were synthesized, and screened for anti-HIV activity against both a non-drug-resistant NL4-3 strain and multiple reverse transcriptas
Structural revision and synthesis of altechromone A
Koenigs,Rinker,Maus,Nieger,Rheinheimer,Waldvogel
supporting information; experimental part, p. 2064 - 2066 (2011/03/20)
The chromone "altechromone A" was synthesized as a substructure in the course of natural product synthesis. Its architecture was verified by X-ray analysis, but spectroscopic data showed a strong deviation from the reported data. By comparison with the sy
