- An efficient synthesis of 4,6 dimethoxyaurones
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4,6-Dimethoxybenzofuran-3(2H)-one was synthesized in two steps starting from phloroglucinol and used as a useful starting block for the synthesis of aurones by condensation with benzaldehyde derivatives.
- Beney, Chantal,Mariotte, Anne-Marie,Boumendjel, Ahce?ne
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- Synthesis and evaluation of 4-hydroxyl aurone derivatives as multifunctional agents for the treatment of Alzheimer's disease
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A series of 4-hydroxyl aurone derivatives were designed synthesized and evaluated as potential multifunctional agents for the treatment of Alzheimer's disease. The results demonstrated that most of the derivatives exhibited good multifunctional properties. Among them, compound 14e displayed good inhibitory activities of self- and Cu2+-induced Aβ1-42 aggregation with 99.2% and 84.0% at 25 μM, respectively, and high antioxidant activity with a value 1.90-fold of Trolox. In addition, 14e also showed remarkable inhibitory activities of both monoamine oxidase A and B with IC50 values of 0.271 μM and 0.393 μM, respectively. However the 6-methoxyl aurones 15a-c revealed excellent selectivity toward MAO-B. Furthermore, the representative compounds 14e and 15b displayed good metal-chelating abilities and blood-brain barrier (BBB) permeabilities in vitro.
- Li, Yan,Qiang, Xiaoming,Luo, Li,Li, Yuxing,Xiao, Ganyuan,Tan, Zhenghuai,Deng, Yong
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- Total synthesis of (±)-Anastatins A and B
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Abstract Two novel flavones (±)-Anastatins A and B, each containing a benzofuran moiety, were synthesized for the first time by using bromination, Suzuki coupling reaction, and an oxidation/Oxa-Michael reaction cascade as the key steps. The syntheses of (±)-Anastatins A and B were achieved in eight steps from the commercially available phloroglucinol with 9% and 10% overall yield, respectively.
- Pan, Guojun,Ma, Yantao,Yang, Ke,Zhao, Xia,Yang, Hui,Yao, Qingwei,Lu, Kui,Zhu, Tao,Yu, Peng
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- Discovery of Novel Apigenin-Piperazine Hybrids as Potent and Selective Poly (ADP-Ribose) Polymerase-1 (PARP-1) Inhibitors for the Treatment of Cancer
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Poly (ADP-ribose) polymerase-1 (PARP-1) is a potential target for the discovery of chemosensitizers and anticancer drugs. Amentoflavone (AMF) is reported to be a selective PARP-1 inhibitor. Here, structural modifications and trimming of AMF have led to a series of AMF derivatives (9a-h) and apigenin-piperazine/piperidine hybrids (14a-p, 15a-p, 17a-h, and 19a-f), respectively. Among these compounds, 15l exhibited a potent PARP-1 inhibitory effect (IC50 = 14.7 nM) and possessed high selectivity to PARP-1 over PARP-2 (61.2-fold). Molecular dynamics simulation and the cellular thermal shift assay revealed that 15l directly bound to the PARP-1 structure. In in vitro and in vivo studies, 15l showed a potent chemotherapy sensitizing effect against A549 cells and a selective cytotoxic effect toward SK-OV-3 cells through PARP-1 inhibition. 15l·2HCl also displayed good ADME characteristics, pharmacokinetic parameters, and a desirable safety margin. These findings demonstrated that 15l·2HCl may serve as a lead compound for chemosensitizers and the (BRCA-1)-deficient cancer therapy.
- Long, Huan,Hu, Xiaolong,Wang, Baolin,Wang, Quan,Wang, Rong,Liu, Shumeng,Xiong, Fei,Jiang, Zhenzhou,Zhang, Xiao-Qi,Ye, Wen-Cai,Wang, Hao
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p. 12089 - 12108
(2021/09/06)
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- COMPOUNDS HAVING HEPATIAL DISEASE EFFECTIVE
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The invention discloses a compound with a hepatopathy curative effect, and the compound is a compound shown as a general formula (I), an optical isomer or pharmaceutically acceptable salt thereof, canbe applied to treatment or prevention of hepatopathy, particularly to drugs for treating or preventing fatty liver, liver fibrosis or liver cirrhosis, and has a good application prospect.
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Paragraph 0167-0169
(2021/01/29)
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- Aurone derivatives as promising antibacterial agents against resistant Gram-positive pathogens
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A set of variously substituted aurones was synthesized and evaluated against Methicillin-Resistant S. aureus (MRSA) and P. aeruginosa. Several analogues were found active against MRSA, but no effect was recorded against P. aeruginosa. Compounds 27, 30 and 33 showed low cytotoxicity, and were tested against a full range of bacterial (Gram-positive and Gram-negative) and fungal species, including resistant strains. These aurones displayed a selective inhibition of Gram-positive bacteria with excellent Therapeutic Index values, while showing no significant action on several Gram-negative strains, H. pylori and V. alginolyticus being the only susceptible strains among the Gram-negative bacteria tested. A permeabilization assay showed that the antibacterial activity of at least some of the aurones could be linked to alterations of the bacterial membrane. Overall, this study endorses the use of the aurone scaffold for the development of new potent and selective antibacterial agents.
- Olleik, Hamza,Yahiaoui, Samir,Roulier, Brayan,Courvoisier-Dezord, Elise,Perrier, Josette,Pérès, Basile,Hijazi, Akram,Baydoun, Elias,Raymond, Josette,Boumendjel, Ahcène,Maresca, Marc,Haudecoeur, Romain
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p. 133 - 141
(2019/01/23)
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- Synthesis of structurally diverse biflavonoids
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Synthetic biflavonoids are associated with interesting biological activities, yet they remain poorly explored within drug discovery. Recent years have witnessed a growing interest in synthetic approaches that can provide access to structurally novel biflavonoids so that the biological usefulness of this compound class can be more fully investigated. Herein, we report upon the exploration of strategies based around Suzuki-Miyaura cross-coupling and alcohol methylenation for the synthesis of two classes of biflavonoids: (i) rare ‘hybrid’ derivatives containing flavonoid monomers belonging to different subclasses, and (ii) homodimeric compounds in which the two flavonoid monomers are linked by a methylenedioxy group. Application of these strategies enabled the preparation of a structurally diverse collection of novel biflavonoids from readily-available starting materials, thereby facilitating the probing of uncharted regions of biologically interesting chemical space.
- Sum, Tze Jing,Sum, Tze Han,Galloway, Warren R.J.D.,Twigg, David G.,Ciardiello, Joe J.,Spring, David R.
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supporting information
p. 5089 - 5101
(2018/05/23)
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- Structure-activity relationship of the inhibitory effects of flavonoids on nitric oxide production in RAW264.7 cells
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We isolated flavonoids from herbal specimens from the Tibetan region (Sophora yunnanensis and Rhodiola sacra) that suppress nitric oxide (NO) production in macrophages stimulated by lipopolysaccharide and interferon-γ. The isolated flavonoids carry symmetric substitutions in the B ring (R3′= R5′). We analyzed the quantitative structure-activity relationship of the inhibitory activity by comparative molecular field analysis (CoMFA) using this series of flavonoids. Use of flavonoids with symmetrical substitutions in the B ring made it simpler to align molecules because it was not necessary to consider a huge number of combinations due to the B-ring conformation. The CoMFA model, whose cross-validated q2value was 0.705, suggested the existence of a hydroxy group at the 5-position, the choice of the A/C-ring scaffold (chromane or chromene) and electrostatic field around the B ring are important for NO inhibitory activity. Flavonoids synthesized based on the CoMFA model exhibited significant inhibitory potential against NO production, validating the predictive capability of the CoMFA model.
- Jiang, Wen-Jun,Daikonya, Akihiro,Ohkawara, Mitsuyoshi,Nemoto, Takashi,Noritake, Ryusuke,Takamiya, Tomoko,Kitanaka, Susumu,Iijima, Hiroshi
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- Design, synthesis and biological evaluation of flavonoid salicylate derivatives as potential anti-tumor agents
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A series of flavonoid salicylate derivatives containing trimethoxybenzene and a series of chrysin salicylate derivatives were synthesized for use as anti-tumor agents, and evaluated for antiproliferative activity using three human tumor cells: MCF-7 (breast carcinoma cells), HepG2 (liver carcinoma cells), MGC-803 (gastric carcinoma cells) and the mice tumor cells MFC (forestomach carcinoma cells). A substituent group of a suitable size and the trimethoxybenzene had a certain influence on the bioactivity of the flavonoid salicylate derivatives. Compound 2 and its salicylate derivatives 7a-7g containing the trimethoxybenzene exhibited more antiproliferative activity. Among them, compound 7g displayed the most potent antiproliferative activity against MGC-803 cells and MFC cells with the concentration causing 50% inhibition of cell growth (IC50) values of 11.05 ± 1.58 μM and 13.73 ± 2.04 μM, respectively. The flow cytometry results showed that compound 7g caused the cell cycle to be arrested in the G0/G1 phase and induced apoptosis of MFC cells in a dose-dependent manner. Furthermore, compound 7g showed good anti-tumor activity in vivo. These results suggested that compound 7g could be a new, potent anti-tumor candidate which should be optimized and evaluated further.
- Deng, Xiangping,Wang, Zhe,Liu, Juan,Xiong, Shujuan,Xiong, Runde,Cao, Xuan,Chen, Yanming,Zheng, Xing,Tang, Guotao
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p. 38171 - 38178
(2017/08/16)
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- A kind of coumarin substituted flavone derivatives and its preparation method and application (by machine translation)
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The invention relates to a flavonoid derivatives of coumarin substituted preparation and its use in medicine for diabetes, the application for the first time to synthesize the coumarin substituted flavonoid compounds, and for the first time on the α - glucosidase inhibitory activity evaluation, the results showed that the coumarin substituted flavonoid compound IC50 30 μm, are better than the acarbose inhibiting activity, found coumarin substituted flavone derivatives can very good inhibition α - glucosidase, at the same time the derivative synthesis, purification method which is simple, in medicine for treating diabetes in the development and application of and has broad prospects. (by machine translation)
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Paragraph 0053; 0055
(2017/09/01)
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- Combinatorial synthesis of structurally diverse triazole-bridged flavonoid dimers and trimers
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Flavonoids are a large family of compounds associated with a broad range of biologically useful properties. In recent years, synthetic compounds that contain two flavonoid units linked together have attracted attention in drug discovery and development projects. Numerous flavonoid dimer systems, incorporating a range of monomers attached via different linkers, have been reported to exhibit interesting bioactivities. From a medicinal chemistry perspective, the 1,2,3-triazole ring system has been identified as a particularly attractive linker moiety in dimeric derivatives (owing to several favourable attributes including proven biological relevance and metabolic stability) and triazole-bridged flavonoid dimers possessing anticancer and antimalarial activities have recently been reported. However, there are relatively few examples of libraries of triazole-bridged flavonoid dimers and the diversity of flavonoid subunits present within these is typically limited. Thus, this compound type arguably remains underexplored within drug discovery. Herein, we report a modular strategy for the synthesis of novel and biologically interesting triazole-bridged flavonoid heterodimers and also very rare heterotrimers from readily available starting materials. Application of this strategy has enabled step-efficient and systematic access to a library of structurally diverse compounds of this sort, with a variety of monomer units belonging to six different structural subclasses of flavonoid successfully incorporated.
- Sum, Tze Han,Sum, Tze Jing,Galloway, Warren R. J. D.,Collins, Súil,Twigg, David G.,Hollfelder, Florian,Spring, David R.
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- Inhibitory effect of flavonoids on human glutaminyl cyclase
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Glutaminyl cyclase (QC) plays an important role in the pathogenesis of Alzheimer's disease (AD) and can be a potential target for the development of novel anti-AD agents. However, the study of QC inhibitors are still less. Here, phenol-4′ (R1-), C5-OH (R2-) and C7-OH (R3-) modified apigenin derivatives were synthesized as a new class of human QC (hQC) inhibitors. The efficacy investigation of these compounds was performed by spectrophotometric assessment and the structure-activity relationship (SAR) was evaluated. Molecular docking was also carried out to analyze the binding mode of the synthesized flavonoid to the active site of hQC.
- Li, Manman,Dong, Yao,Yu, Xi,Zou, Yongdong,Zheng, Yizhi,Bu, Xianzhang,Quan, Junmin,He, Zhendan,Wu, Haiqiang
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p. 2280 - 2286
(2016/04/26)
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- B-ring modified aurones as promising allosteric inhibitors of hepatitis C virus RNA-dependent RNA polymerase
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Following our recent report showing the potential of naturally occurring aurones (2-benzylidenebenzofuran-3(2H)-ones) as anti-hepatitis C virus (HCV) agents, efforts were continued in order to refine the structural requirements for the inhibitory effect on HCV RNA-dependent RNA polymerase (RdRp). In this study, we targeted the B-ring moiety of aurones with the aim to improve structural features associated with higher inhibition of the targeted polymerase. In vitro evaluation of the RdRp inhibitory activity of the 37 newly synthesized compounds pointed out that the replacement of the B-ring with an N-substituted indole moiety induced the highest inhibitory effect. Of these, compounds 31, 40 and 41 were found to be the most active (IC50 = 2.3-2.4 μM). Docking experiments performed with the most active compounds revealed that the allosteric thumb pocket I of RdRp is the binding pocket for aurone analogues.
- Meguellati, Amel,Ahmed-Belkacem, Abdelhakim,Yi, Wei,Haudecoeur, Romain,Crouillère, Marie,Brillet, Rozenn,Pawlotsky, Jean-Michel,Boumendjel, Ahcène,Peuchmaur, Marine
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p. 579 - 592
(2014/06/09)
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- Synthesis and anti-cancer activities of apigenin derivatives
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A novel series of apigenin derivatives with phloroglucinol or resorcinol as raw materials were synthesized according to Baker-Venaktaraman reaction and their in vitro inhibitory activities on colorectal adenocarcinoma (HT-29) and leucocythemia (HL-60) cell lines were evaluated by the standard methyl thiazole tetrazolium (MTT) method. The results of biological test showed that some of apigenin derivatives possessed stronger anti-cancer activities than apigenin. Compound 6 showed the strongest activity against colorectal adenocarcinoma (HT-29) and leucocythemia (HL-60) cell lines with IC50 valure of 2.03±0.22 μM, 2.25±0.42 μM, it was better than 5-FU (12.92±0.61 μM, 9.56±0.16 μM), which shows a potezntial compound for colorectal adenocarcinoma and leucocythemia.
- Zheng, Xing,Yu, Liuying,Yang, Jing,Yao, Xu,Yan, Wenna,Bo, Shaowei,Liu, Ya,Wei, Yun,Wu, Zhiyi,Wang, Guan
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p. 747 - 752
(2015/04/14)
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- Discovery of naturally occurring aurones that are potent allosteric inhibitors of hepatitis C virus RNA-dependent RNA polymerase
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We have identified naturally occurring 2-benzylidenebenzofuran-3-ones (aurones) as new templates for non-nucleoside hepatitis C virus (HCV) RNA-dependent RNA polymerase (RdRp) inhibitors. The aurone target site, identified by site-directed mutagenesis, is located in thumb pocket I of HCV RdRp. The RdRp inhibitory activity of 42 aurones was rationally explored in an enzyme assay. Molecular docking studies were used to determine how aurones bind to HCV RdRp and to predict their range of inhibitory activity. Seven aurone derivatives were found to have potent inhibitory effects on HCV RdRp, with IC50 below 5 μM and excellent selectivity index (inhibition activity versus cellular cytotoxicity). The most active aurone analogue was (Z)-2-((1-butyl-1H-indol-3-yl)methylene)-4,6-dihydroxybenzofuran-3(2H)-one (compound 51), with an IC50 of 2.2 μM. Their potent RdRp inhibitory activity and their low toxicity make these molecules attractive candidates as direct-acting anti-HCV agents.
- Haudecoeur, Romain,Ahmed-Belkacem, Abdelhakim,Yi, Wei,Fortuné, Antoine,Brillet, Rozenn,Belle, Catherine,Nicolle, Edwige,Pallier, Coralie,Pawlotsky, Jean-Michel,Boumendjel, Ahcène
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scheme or table
p. 5395 - 5402
(2011/10/02)
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- Functionalized aurones as inducers of NAD(P)H:quinone oxidoreductase 1 that activate AhR/XRE and Nrf2/ARE signaling pathways: Synthesis, evaluation and SAR
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The chemopreventive potential of functionalized aurones and related compounds as inducers of NAD(P)H:quinone oxidoreductase 1 (NQO1, EC 1.6.99.2) are described. Several 4,6-dimethoxy and 5-hydroxyaurones induced NQO1 activity of Hepa1c1c7 cells by 2-fold at submicromolar concentrations, making these the most potent inducers to be identified from this class. Mechanistically, induction of NQO1 was mediated by the activation of AhR/XRE and Nrf2/ARE pathways, indicating that aurones may be mixed activators of NQO1 induction or agents capable of exploiting the proposed cross-talk between the AhR and Nrf2 gene batteries. QSAR analysis by partial least squares projection to latent structures (PLS) identified size parameters, in particular those associated with non-polar surface areas, as an important determinant of induction activity. These were largely determined by the substitution on rings A and B. A stereoelectronic role for the exocyclic double bond as reflected in the E LUMO term was also identified. The electrophilicity of the double bond or its effect on the conformation of the target compound are possible key features for induction activity.
- Lee, Chong-Yew,Chew, Eng-Hui,Go, Mei-Lin
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scheme or table
p. 2957 - 2971
(2010/09/03)
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- Synthesis and evaluation of derrubone and select analogues
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(Chemical Equation Presented) Recently, we reported that the natural product derrubone exhibits Hsp90 inhibitory activity. Due to its unique architectural scaffold and proposed rapid assembly, the synthesis of this natural product was pursued with the aim of identifying structure-activity relationships. Synthesis of the natural product was accomplished in eight highly convergent steps, which led to a facile method for the construction of related compounds. Biological evaluation of derrubone and its analogues identified several compounds that exhibit low micromolar inhibitory activity against breast and colon cancer cell lines.
- Hastings, Jedidiah M.,Hadden, M. Kyle,Blagg, Brian S. J.
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p. 369 - 373
(2008/09/17)
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- DPPH radical scavenging reaction of hydroxy- and methoxychalcones
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The DPPH radical scavenging activity of 2′,4′,6′- trihydroxy- and 2′-hydroxy-4′,6′-dimethoxychalcones carrying a 2,3- and 3,4-dihydroxylated, and 3,4,5-trihydroxylated B-ring was evaluated in alcoholic and non-alcoholic solvents. All test compounds scavenged more than two equivalent of radicals by a possible conversion to the corresponding B-ring quinones and in most cases subsequently underwent cyclization to aurones and flavanones, these being identified in the reaction solutions by an in situ NMR analysis. Interestingly, the reaction between 2′,3,4-trihydroxy-4′, 6′-dimethoxychalcone and the DPPH radical was significantly affected by the solvent used, which might be accounted for by the difference in readiness for cyclization to an aurone.
- Nishida, Jun,Kawabata, Jun
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p. 193 - 202
(2008/02/09)
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- A method of cosmetic depigmentation care by applying at least one aurone
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At least one aurone or a natural or synthetic derivative of aurone, or an analogue of aurone, in which the independent phenyl ring can be substituted by a heterocycle of pyrrole, imidazole, triazole, pyridine, furan, or thiophene type, is disclosed as a cosmetic agent, or as an active substance, for the manufacture either of a cosmetic composition, or of a pharmaceutical composition, notably a dermatological composition, having a melanogenesis-inhibiting activity or a depigmenting activity, or an anti-tyrosinase activity.
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Page/Page column 8-9
(2008/06/13)
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- Preparation of 4,6,3',4'-tetrasubstituted aurones via aluminium oxide-catalyzed condensation
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4,6,3',4'-Tetrasubstituted aurones were prepared by a protection- deprotection route with an alumina-catalyzed condensation of 3(2H)-benzofuranones with substituted aldehydes as the key step. Aureusidin (6) was obtained by demethylation of 4,6,3',4'-tetramethoxyaurone (5), a natural product from Cyperus capitatus. 4,6,3',4'-Tetrabenzyloxyaurone (9) was converted in a one hydrogenation-deprotection step to dihydroaureusidin (10).
- Bolek, David,Guetschow, Michael
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p. 1399 - 1403
(2007/10/03)
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- Synthesis of gem-difluoromethylenated biflavonoid via the Suzuki coupling reaction
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gem-Difluoromethylenated biflavonoid 1 was synthesized via the Suzuki coupling reaction. The key intermediate 6-iodonated flavone 4 was regioselectively synthesized by the use of AgOAc/I2 under mild conditions without handling of a strongly toxic reagent. The key step was the formation of a flavone 3′-boronate 3 using a palladium-catalyzed exchange of the corresponding 3′-iodonated flavone with a diboron reagent.
- Zheng, Xing,Meng, Wei-Dong,Qing, Feng-Ling
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p. 8083 - 8085
(2007/10/03)
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- Synthesis and anticancer effect of B-ring trifluoromethylated flavonoids
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A series of B-ring trifluoromethylated flavonoids derivatives were prepared and tested in vitro against human gastric adenocarcinoma cell line (SGC-7901). Among these derivatives, 5,7-dipropoxy-2-(4′ -trifluoromethylphenyl)-chromen-4-one 5c had the strongest activity against SGC-7901 cell.
- Zheng, Xing,Cao, Jian-Guo,Meng, Wei-Dong,Qing, Feng-Ling
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p. 3423 - 3427
(2007/10/03)
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- 4-Hydroxy-6-methoxyaurones with high-affinity binding to cytosolic domain of P-glycoprotein
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A series of 4-hydroxy-6-methoxyaurones and 4,6-dimethoxyaurones has been synthesised and tested for their binding affinity toward the nucleotide-binding domain of P-glycoprotein, an ABC (ATP-Binding Cassette) transporter which mediates the resistance of cancer cells to chemotherapy. These compounds differ from each other by the nature of the substituent on the aurone B-ring. The binding affinity seems to be linked to the nature of the substituent, as well as to the presence or the absence of a hydroxy group at position 4. The most active compounds were 4′-bromo-4-hydroxy-6-methoxyaurone and 4-hydroxy-4′-iodo-6-methoxyaurone.
- Boumendjel, Ahcene,Beney, Chantal,Deka, Nabajyoti,Mariotte, Anne-Marie,Lawson, Martin Ata,Trompier, Doriane,Baubichon-Cortay, Helene,Di Pietro, Attilio
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p. 854 - 856
(2007/10/03)
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