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Fernanda Borges - One of the best experts on this subject based on the ideXlab platform.
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Tight-Binding Inhibition of Human Monoamine Oxidase B by Chromone Analogs: A Kinetic, Crystallographic, and Biological Analysis
Journal of Medicinal Chemistry, 2018Co-Authors: Joana Reis, Fernando Cagide, Fernanda Borges, Nicola Manzella, Jeanne Mialet-perez, Eugenio Uriarte, Angelo Parini, Andrea Mattevi, Claudia BindaAbstract:Monoamine oxidase B (MAO-B) is a validated drug target for Parkinson's disease. Chromone derivatives were identified as novel potent and reversible MAO-B inhibitors, and herewith we report on a crystallographic and biochemical analysis to investigate their inhibition mechanism. The crystal structures of human MAO-B in complex with three Chromone analogs bearing different substituents on the exocyclic aromatic ring (determined at 1.6-1.8 Å resolution) showed that they all bind in the active site cavity of the protein with the Chromone moiety located in front of the FAD cofactor. These inhibitors form two hydrogen bonds with Tyr435 and Cys172 and perfectly fit the hydrophobic flat active site of human MAO-B. This is reflected in their tight-binding mechanism of inhibition with Ki values of 55, 17, and 31 nM for N-(3',4'-dimethylphenyl)-4-oxo-4 H-chromene-3-carboxamide (1), N-(3'-chlorophenyl)-4-oxo-4 H-chromene-3-carboxamide (2), and N-(3'-fluorophenyl)-4-oxo-4 H-chromene-3-carboxamide (3), respectively. These compounds were also 1000-fold more effective than l-deprenyl in reducing the cellular levels of reactive oxygen species (ROS).
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tight binding inhibition of human monoamine oxidase b by Chromone analogs a kinetic crystallographic and biological analysis
Journal of Medicinal Chemistry, 2018Co-Authors: Joana Reis, Fernando Cagide, Fernanda Borges, Nicola Manzella, Eugenio Uriarte, Angelo Parini, Jeanne Mialetperez, Claudia BindaAbstract:Monoamine oxidase B (MAO-B) is a validated drug target for Parkinson’s disease. Chromone derivatives were identified as novel potent and reversible MAO-B inhibitors, and herewith we report on a crystallographic and biochemical analysis to investigate their inhibition mechanism. The crystal structures of human MAO-B in complex with three Chromone analogs bearing different substituents on the exocyclic aromatic ring (determined at 1.6–1.8 A resolution) showed that they all bind in the active site cavity of the protein with the Chromone moiety located in front of the FAD cofactor. These inhibitors form two hydrogen bonds with Tyr435 and Cys172 and perfectly fit the hydrophobic flat active site of human MAO-B. This is reflected in their tight-binding mechanism of inhibition with Ki values of 55, 17, and 31 nM for N-(3′,4′-dimethylphenyl)-4-oxo-4H-chromene-3-carboxamide (1), N-(3′-chlorophenyl)-4-oxo-4H-chromene-3-carboxamide (2), and N-(3′-fluorophenyl)-4-oxo-4H-chromene-3-carboxamide (3), respectively. These...
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Tight-Binding Inhibition of Human Monoamine Oxidase B by Chromone Analogs: A Kinetic, Crystallographic, and Biological Analysis
2018Co-Authors: Joana Reis, Fernando Cagide, Fernanda Borges, Nicola Manzella, Jeanne Mialet-perez, Eugenio Uriarte, Angelo Parini, Claudia BindaAbstract:Monoamine oxidase B (MAO-B) is a validated drug target for Parkinson’s disease. Chromone derivatives were identified as novel potent and reversible MAO-B inhibitors, and herewith we report on a crystallographic and biochemical analysis to investigate their inhibition mechanism. The crystal structures of human MAO-B in complex with three Chromone analogs bearing different substituents on the exocyclic aromatic ring (determined at 1.6–1.8 Å resolution) showed that they all bind in the active site cavity of the protein with the Chromone moiety located in front of the FAD cofactor. These inhibitors form two hydrogen bonds with Tyr435 and Cys172 and perfectly fit the hydrophobic flat active site of human MAO-B. This is reflected in their tight-binding mechanism of inhibition with Ki values of 55, 17, and 31 nM for N-(3′,4′-dimethylphenyl)-4-oxo-4H-chromene-3-carboxamide (1), N-(3′-chlorophenyl)-4-oxo-4H-chromene-3-carboxamide (2), and N-(3′-fluorophenyl)-4-oxo-4H-chromene-3-carboxamide (3), respectively. These compounds were also 1000-fold more effective than l-deprenyl in reducing the cellular levels of reactive oxygen species (ROS)
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Chromone as a Privileged Scaffold in Drug Discovery: Recent Advances
Journal of medicinal chemistry, 2017Co-Authors: Joana Reis, Alexandra Gaspar, Nuno Milhazes, Fernanda BorgesAbstract:The use of privileged structures in drug discovery has proven to be an effective strategy, allowing the generation of innovative hits/leads and successful optimization processes. Chromone is recognized as a privileged structure and a useful template for the design of novel compounds with potential pharmacological interest, particularly in the field of neurodegenerative, inflammatory, and infectious diseases as well as diabetes and cancer. This perspective provides the reader with an update of an earlier article entitled “Chromone: A Valid Scaffold in Medicinal Chemistry” (Chem. Rev. 2014, 114, 4960−4992) and is mainly focused on Chromones of biological interest, including those isolated from natural sources. Moreover, as drug repurposing is becoming an attractive drug discovery approach, recent repurposing studies of Chromone-based drugs are also reported.
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synthesis of 6 aryl heteroaryl 4 oxo 4h chromene 2 carboxylic ethyl ester derivatives
Tetrahedron Letters, 2016Co-Authors: Carlos Fernandes, Alexandra Gaspar, Ligia R. Gomes, John N. Low, P Soares, Diana Martins, Fernanda BorgesAbstract:Abstract The development of new chemical entities represents an important challenge in pharmaceutical industry, being the use of privileged scaffolds for library design and drug discovery a valuable approach. Among the panoply of privileged structures, our research group has focused its attention on the Chromone (4 H -benzopyran-4-one) scaffold due to its chemical versatility and ability to bind to multiple targets. With this endeavour we report an expedite two-step procedure for the synthesis of novel 6-aryl/heteroaryl-4-oxo-4 H -chromene-2-carboxylic ethyl ester. The new Chromones were synthesized by a C–C Suzuki cross-coupling microwave-assisted reaction, using Pd(OAc) 2 as a catalyst, and a classic Claisen condensation followed by an intramolecular cyclization process.
Joana Reis - One of the best experts on this subject based on the ideXlab platform.
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Tight-Binding Inhibition of Human Monoamine Oxidase B by Chromone Analogs: A Kinetic, Crystallographic, and Biological Analysis
Journal of Medicinal Chemistry, 2018Co-Authors: Joana Reis, Fernando Cagide, Fernanda Borges, Nicola Manzella, Jeanne Mialet-perez, Eugenio Uriarte, Angelo Parini, Andrea Mattevi, Claudia BindaAbstract:Monoamine oxidase B (MAO-B) is a validated drug target for Parkinson's disease. Chromone derivatives were identified as novel potent and reversible MAO-B inhibitors, and herewith we report on a crystallographic and biochemical analysis to investigate their inhibition mechanism. The crystal structures of human MAO-B in complex with three Chromone analogs bearing different substituents on the exocyclic aromatic ring (determined at 1.6-1.8 Å resolution) showed that they all bind in the active site cavity of the protein with the Chromone moiety located in front of the FAD cofactor. These inhibitors form two hydrogen bonds with Tyr435 and Cys172 and perfectly fit the hydrophobic flat active site of human MAO-B. This is reflected in their tight-binding mechanism of inhibition with Ki values of 55, 17, and 31 nM for N-(3',4'-dimethylphenyl)-4-oxo-4 H-chromene-3-carboxamide (1), N-(3'-chlorophenyl)-4-oxo-4 H-chromene-3-carboxamide (2), and N-(3'-fluorophenyl)-4-oxo-4 H-chromene-3-carboxamide (3), respectively. These compounds were also 1000-fold more effective than l-deprenyl in reducing the cellular levels of reactive oxygen species (ROS).
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tight binding inhibition of human monoamine oxidase b by Chromone analogs a kinetic crystallographic and biological analysis
Journal of Medicinal Chemistry, 2018Co-Authors: Joana Reis, Fernando Cagide, Fernanda Borges, Nicola Manzella, Eugenio Uriarte, Angelo Parini, Jeanne Mialetperez, Claudia BindaAbstract:Monoamine oxidase B (MAO-B) is a validated drug target for Parkinson’s disease. Chromone derivatives were identified as novel potent and reversible MAO-B inhibitors, and herewith we report on a crystallographic and biochemical analysis to investigate their inhibition mechanism. The crystal structures of human MAO-B in complex with three Chromone analogs bearing different substituents on the exocyclic aromatic ring (determined at 1.6–1.8 A resolution) showed that they all bind in the active site cavity of the protein with the Chromone moiety located in front of the FAD cofactor. These inhibitors form two hydrogen bonds with Tyr435 and Cys172 and perfectly fit the hydrophobic flat active site of human MAO-B. This is reflected in their tight-binding mechanism of inhibition with Ki values of 55, 17, and 31 nM for N-(3′,4′-dimethylphenyl)-4-oxo-4H-chromene-3-carboxamide (1), N-(3′-chlorophenyl)-4-oxo-4H-chromene-3-carboxamide (2), and N-(3′-fluorophenyl)-4-oxo-4H-chromene-3-carboxamide (3), respectively. These...
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Tight-Binding Inhibition of Human Monoamine Oxidase B by Chromone Analogs: A Kinetic, Crystallographic, and Biological Analysis
2018Co-Authors: Joana Reis, Fernando Cagide, Fernanda Borges, Nicola Manzella, Jeanne Mialet-perez, Eugenio Uriarte, Angelo Parini, Claudia BindaAbstract:Monoamine oxidase B (MAO-B) is a validated drug target for Parkinson’s disease. Chromone derivatives were identified as novel potent and reversible MAO-B inhibitors, and herewith we report on a crystallographic and biochemical analysis to investigate their inhibition mechanism. The crystal structures of human MAO-B in complex with three Chromone analogs bearing different substituents on the exocyclic aromatic ring (determined at 1.6–1.8 Å resolution) showed that they all bind in the active site cavity of the protein with the Chromone moiety located in front of the FAD cofactor. These inhibitors form two hydrogen bonds with Tyr435 and Cys172 and perfectly fit the hydrophobic flat active site of human MAO-B. This is reflected in their tight-binding mechanism of inhibition with Ki values of 55, 17, and 31 nM for N-(3′,4′-dimethylphenyl)-4-oxo-4H-chromene-3-carboxamide (1), N-(3′-chlorophenyl)-4-oxo-4H-chromene-3-carboxamide (2), and N-(3′-fluorophenyl)-4-oxo-4H-chromene-3-carboxamide (3), respectively. These compounds were also 1000-fold more effective than l-deprenyl in reducing the cellular levels of reactive oxygen species (ROS)
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Chromone as a Privileged Scaffold in Drug Discovery: Recent Advances
Journal of medicinal chemistry, 2017Co-Authors: Joana Reis, Alexandra Gaspar, Nuno Milhazes, Fernanda BorgesAbstract:The use of privileged structures in drug discovery has proven to be an effective strategy, allowing the generation of innovative hits/leads and successful optimization processes. Chromone is recognized as a privileged structure and a useful template for the design of novel compounds with potential pharmacological interest, particularly in the field of neurodegenerative, inflammatory, and infectious diseases as well as diabetes and cancer. This perspective provides the reader with an update of an earlier article entitled “Chromone: A Valid Scaffold in Medicinal Chemistry” (Chem. Rev. 2014, 114, 4960−4992) and is mainly focused on Chromones of biological interest, including those isolated from natural sources. Moreover, as drug repurposing is becoming an attractive drug discovery approach, recent repurposing studies of Chromone-based drugs are also reported.
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Discovery of two new classes of potent monoamine oxidase-B inhibitors by tricky chemistry
Chemical Communications, 2015Co-Authors: Fernando Cagide, Tiago H. Silva, Joana Reis, Alexandra Gaspar, Fernanda Borges, Ligia R. Gomes, John N. LowAbstract:The discovery of potent and selective monoamine oxidase-B inhibitors for the management of neurodegenerative diseases such as Alzheimer’s and Parkinson’s diseases is still a challenging endeavor. Herein, we report the discovery of two new classes of potent and selective MAO-B inhibitors based on chromane-2,4-dione and Chromone-3-carboxamide scaffolds.
Alexandra Gaspar - One of the best experts on this subject based on the ideXlab platform.
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Chromone as a Privileged Scaffold in Drug Discovery: Recent Advances
Journal of medicinal chemistry, 2017Co-Authors: Joana Reis, Alexandra Gaspar, Nuno Milhazes, Fernanda BorgesAbstract:The use of privileged structures in drug discovery has proven to be an effective strategy, allowing the generation of innovative hits/leads and successful optimization processes. Chromone is recognized as a privileged structure and a useful template for the design of novel compounds with potential pharmacological interest, particularly in the field of neurodegenerative, inflammatory, and infectious diseases as well as diabetes and cancer. This perspective provides the reader with an update of an earlier article entitled “Chromone: A Valid Scaffold in Medicinal Chemistry” (Chem. Rev. 2014, 114, 4960−4992) and is mainly focused on Chromones of biological interest, including those isolated from natural sources. Moreover, as drug repurposing is becoming an attractive drug discovery approach, recent repurposing studies of Chromone-based drugs are also reported.
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synthesis of 6 aryl heteroaryl 4 oxo 4h chromene 2 carboxylic ethyl ester derivatives
Tetrahedron Letters, 2016Co-Authors: Carlos Fernandes, Alexandra Gaspar, Ligia R. Gomes, John N. Low, P Soares, Diana Martins, Fernanda BorgesAbstract:Abstract The development of new chemical entities represents an important challenge in pharmaceutical industry, being the use of privileged scaffolds for library design and drug discovery a valuable approach. Among the panoply of privileged structures, our research group has focused its attention on the Chromone (4 H -benzopyran-4-one) scaffold due to its chemical versatility and ability to bind to multiple targets. With this endeavour we report an expedite two-step procedure for the synthesis of novel 6-aryl/heteroaryl-4-oxo-4 H -chromene-2-carboxylic ethyl ester. The new Chromones were synthesized by a C–C Suzuki cross-coupling microwave-assisted reaction, using Pd(OAc) 2 as a catalyst, and a classic Claisen condensation followed by an intramolecular cyclization process.
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Discovery of two new classes of potent monoamine oxidase-B inhibitors by tricky chemistry
Chemical Communications, 2015Co-Authors: Fernando Cagide, Tiago H. Silva, Joana Reis, Alexandra Gaspar, Fernanda Borges, Ligia R. Gomes, John N. LowAbstract:The discovery of potent and selective monoamine oxidase-B inhibitors for the management of neurodegenerative diseases such as Alzheimer’s and Parkinson’s diseases is still a challenging endeavor. Herein, we report the discovery of two new classes of potent and selective MAO-B inhibitors based on chromane-2,4-dione and Chromone-3-carboxamide scaffolds.
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A comparison of the structures of some 2- and 3-substituted Chromone derivatives: a structural study on the importance of the secondary carboxamide backbone for the inhibitory activity of MAO-B
International Union of Crystallography, 2015Co-Authors: Ligia R. Gomes, Fernando Cagide, Alexandra Gaspar, John Nicolson Low, Fernanda BorgesAbstract:The crystal structures of the 3-substituted tertiary Chromone carboxamide derivative, C17H13NO3, N-methyl-4-oxo-N-phenyl-4H-chromene-3-carboxamide (1), and the Chromone carbonyl pyrrolidine derivatives, C14H13NO3, 3-(pyrrolidine-1-carbonyl)-4H-chromen-4-one (3) and 2-(pyrrolidine-1-carbonyl)-4H-chromen-4-one (4) have been determined. Their structural features are discussed and compared with similar compounds namely with respect to their MAO-B inhibitory activities. The Chromone carboxamide presents a –syn conformation with the aromatic rings twisted with respect to each other [the dihedral angle between the mean planes of the Chromone system and the exocyclic phenyl ring is 58.48 (8)°]. The pyrrolidine derivatives also display a significant twist: the dihedral angles between the Chromone system and the best plane formed by the pyrrolidine atoms are 48.9 (2) and 23.97 (12)° in (3) and (4), respectively. Compound (3) shows a short C—H...O intramolecular contact forming an S(7) ring. The supramolecular structures for each compound are defined by weak C—H...O hydrogen bonds, which link the molecules into chains and sheets. The Cambridge Structural Database gave 45 hits for compounds with a pyrrolidinecarbonyl group. A simple statistical analysis of their geometric parameters is made in order to compare them with those of the molecules determined in the present work
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Discovery of novel A3 adenosine receptor ligands based on Chromone scaffold.
Biochemical pharmacology, 2012Co-Authors: Alexandra Gaspar, Joana Reis, Eugenio Uriarte, Sonja Kachler, Silvia Paoletta, Karl-norbert Klotz, Stefano Moro, Fernanda BorgesAbstract:Abstract A project focused on the discovery of new chemical entities (NCEs) as AR ligands that incorporate a benzo-γ-pyrone [(4H)-1-benzopyran-4-one] substructure has been developed. Accordingly, two series of novel Chromone carboxamides placed at positions C2 (compounds 2 – 13 ) and C3 (compounds 15 – 26 ) of the γ-pyrone ring were synthesized using Chromone carboxylic acids (compounds 1 or 14 ) as starting materials. From this study and on the basis of the obtained structure–activity relationships it was concluded that the Chromone carboxamide scaffold represent a novel class of AR ligands. The most remarkable Chromones were compounds 21 and 26 that present a better affinity for A 3 AR ( K i = 3680 nM and K i = 3750 nM, respectively). Receptor-driven molecular modeling studies provide information on the binding/selectivity data of the Chromone. The data so far acquired are instrumental for future optimization of Chromone carboxamide as a selective A 3 AR antagonist.
Hao-fu Dai - One of the best experts on this subject based on the ideXlab platform.
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2-(2-Phenylethyl)Chromone derivatives: Promising α-glucosidase inhibitors in agarwood from Aquilaria filaria.
Phytochemistry, 2020Co-Authors: Jing-zhe Yuan, Hao Wang, Wen-li Mei, Li Yang, Man-man Zhu, Wei Yanmei, Wen-xing Long, Hao-fu DaiAbstract:Abstract Twelve undescribed 2-(2-phenylethyl)Chromone derivatives, including one pair of enantiomers, together with eleven known ones, were isolated from the EtOAc extract of agarwood originating from Aquilaria filaria. All structures were elucidated by spectroscopic (NMR, UV, IR, MS) methods and compared with reported data in literatures. Twenty-one compounds were assessed for α-glucosidase inhibitory activity, which showed inhibition of α-glucosidase with IC50 values ranging between 7.8 ± 0.3 to 137.7 ± 3.0 μM (Acarbose, 743.4 ± 3.3 μM; Genistein, 8.3 ± 0.1 μM). Our results expanded the structural diversity of 2-(2-phenylethyl)Chromones from agarwood, and revealed the potential of 2-(2-phenylethyl)Chromones as α-glucosidase inhibitors.
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LC-MS guided identification of dimeric 2-(2-phenylethyl)Chromones and sesquiterpene-2-(2-phenylethyl)Chromone conjugates from agarwood of Aquilaria crassna and their cytotoxicity
Fitoterapia, 2019Co-Authors: Lulu Xia, Hao Wang, Wen-li Mei, Caihong Cai, Li Yang, Hui-qin Chen, Bei Jiang, Yi-ling Yang, Hao-fu DaiAbstract:Abstract Four previously unreported dimeric 2-(2-phenylethyl)Chromones (1–4a) and three unprecedented sesquiterpene-2-(2-phenylethyl)Chromone conjugates (5–7), comprising a sesquiterpenoid and a 5,6,7,8-tetrahydroxy-2-(2-phenylethyl)-5,6,7,8 -tetrahydro-4H-Chromone moiety, as well as three known dimeric 2-(2-phenylethyl)Chromones (4b, 8a, 8b) were identified from agarwood originating from Aquilaria crassna in Cambodia by LC-MS guided separation. Their structures were elucidated by extensive NMR techniques, HRESIMS and CD. All compounds were evaluated for their cytotoxicity against four human cancer cell lines. Compounds 6, 7, 8a, 8b displayed a range of cytotoxic activities with IC50 values in the rang 10.93–49.0 μM
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one new 2 2 phenylethyl Chromone derivative from agarwood of aquilaria crassna in cambodia
Phytochemistry Letters, 2019Co-Authors: Lulu Xia, Hao Wang, Wen-hua Dong, Wen-li Mei, Cui-juan Gai, Caihong Cai, Li Yang, Hao-fu DaiAbstract:Abstract One new 2-(2-phenylethyl)Chromone (1), three new naturally occurring 2-(2-phenylethenyl)Chromones (3–5), together with a known 2-(2-phenylethyl)Chromone (2) were isolated from the EtOH extract of agarwood originating from Aquilaria crassna in Cambodia. Their structures were unambiguously elucidated by detailed spectroscopic (NMR, UV, IR, MS) analyses. All the compounds were tested for acetylcholinesterase (AChE) inhibitory activity and cytotoxicity against tumor cell lines (K562, BEL-7402, SGC-7901 and Hela). Compound 1 displayed weak AChE inhibitory activity (inhibitory ratio: 35.0 ± 2.19%) and cytotoxicity against K562 tumor cell line (IC50: 40.81 ± 0.64 μM). Along with, compound 3 showed cytotoxicity against BEL-7402 tumor cell line (IC50: 44.18 ± 0.34 μM).
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2-(2-phenylethyl)Chromone derivatives from Chinese agarwood induced by artificial holing.
Fitoterapia, 2014Co-Authors: Caihong Cai, Hao Wang, Zhi-kai Guo, Wen-hua Dong, Wen-li Mei, Hao-fu DaiAbstract:Abstract Three new 2-(2-phenylethyl)Chromone derivatives ( 1 – 3 ), together with thirteen known ones ( 4 – 16 ), were isolated from the EtOAc extract of Chinese agarwood induced by artificial holing, originating from Aquilaria sinensis (Lour.) Gilg (Thymelaeaceae). The chemical structures of the new compounds were identified by spectroscopic techniques (UV, IR, MS, 1D and 2D NMR). Compounds 1 , 6 , 15 and 16 exhibited inhibitory effects on Staphylococcus aureus , and compounds 15 and 16 showed inhibitory effects on Ralstonia solanacearum . Compounds 1 – 3 , 7 , 9 , 11 , 12 , 15 and 16 exhibited acetylcholinesterase inhibitory activity. A possible biogenetic pathway of compounds 1 – 16 was proposed to show the relationships between diepoxy-tetrahydro-2-(2-phenylethyl)Chromones, epoxy-tetrahydro-2-(2-phenylethyl) Chromones, tetrahydro-2-(2-phenylethyl)Chromones, and 2-(2-phenylethyl)Chromones of the flidersia type, the four main types of 2-(2-phenylethyl)Chromones found in agarwood, on the basis of their appearances in different stage of agarwood formation.
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A new 2-(2-phenylethyl)Chromone derivative in Chinese agarwood 'Qi-Nan' from Aquilaria sinensis.
Journal of Asian natural products research, 2014Co-Authors: De-lan Yang, Hao Wang, Zhi-kai Guo, Wen-hua Dong, Wen-li Mei, Hao-fu DaiAbstract:Phytochemical analysis of the high quality Chinese agarwood 'Qi-Nan' originating from Aquilaria sinensis (Lour.) Glig led to the isolation of a new 2-(2-phenylethyl)Chromone derivative, qinanones G (1), and four known 2-(2-phenylethyl)Chromones (2-5). Their structures were elucidated by spectroscopic techniques (UV, IR, 1D and 2D NMR) and MS analyses. The NMR data of Chromones 1-3 were first reported, and Chromones 2 and 3 showed weak inhibitory activity against acetylcholinesterase.
Artur M S Silva - One of the best experts on this subject based on the ideXlab platform.
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First intramolecular Diels–Alder reactions using Chromone derivatives: synthesis of chromeno[3,4-b]xanthones and 2-(benzo[c]chromenyl)Chromones
New Journal of Chemistry, 2018Co-Authors: Hélio M. T. Albuquerque, Clementina M.m. Santos, José A. S. Cavaleiro, Artur M S SilvaAbstract:A series of novel (E)-2-(2-propargyloxystyryl)Chromones and (E,E)-2-[4-(2-propargyloxyphenyl)buta-1,3-dien-1-yl]Chromones were designed and synthesized via aldol condensation of 2-methylChromones with 2-propargyloxy(benzaldehyde and cinnamaldehyde), respectively. Both Chromone derivatives were used as substrates in microwave-assisted intramolecular Diels–Alder reactions, affording chromeno[3,4-b]xanthones and 2-(benzo[c]chromenyl)Chromones. This is the first report involving Chromone derivatives in intramolecular Diels–Alder reactions for the synthesis of new oxygen heterocycles, namely xanthone- and flavone-type compounds.
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Synthesis of Chromone-Related Pyrazole Compounds.
Molecules (Basel Switzerland), 2017Co-Authors: Clementina M.m. Santos, Vera L. M. Silva, Artur M S SilvaAbstract:Chromones, six-membered oxygen heterocycles, and pyrazoles, five-membered two-adjacent-nitrogen-containing heterocycles, represent two important classes of biologically active compounds. Certain derivatives of these scaffolds play an important role in medicinal chemistry and have been extensively used as versatile building blocks in organic synthesis. In this context, we will discuss the most relevant advances on the chemistry that involves both Chromone and pyrazole rings. The methods reviewed include the synthesis of Chromone-pyrazole dyads, synthesis of Chromone-pyrazole-fused compounds, and Chromones as starting materials in the synthesis of 3(5)-(2-hydroxyaryl)pyrazoles, among others. This review will cover the literature on the Chromone and pyrazole dual chemistry and their outcomes in the 21st century.
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Chromones a promising ring system for new anti inflammatory drugs
ChemMedChem, 2016Co-Authors: Carlos F M Silva, Diana C G A Pinto, Artur M S SilvaAbstract:The quest for safer anti-inflammatory drugs is still the focus of several medicinal chemistry programs. Chromones (4H-chromen-4-ones) are a group of naturally occurring compounds ubiquitous in plants, and the Chromone core has proven to be a privileged scaffold in medicinal chemistry. Herein we provide an overview of the relevance of Chromones as anti-inflammatory agents, specifically as inhibitors of cyclooxygenase (COX), 5-lipoxygenase (5-LOX), interleukin-5 (IL-5), and nitric oxide (.NO) production. Numerous structure–activity relationships and mechanisms of action are discussed. This review is therefore intended to provide a foundation for the design and synthesis of novel Chromone-based compound libraries for further development into safer and more efficient anti-inflammatory agents.
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actions of bisnucleophiles on e 3 3 2 hydroxyaryl 3 oxoprop 1 en 1 yl Chromones versatile transformations into oxygen and nitrogen containing heterocycles
Synlett, 2015Co-Authors: Ridha Hassaine, Oualid Talhi, Okkacha Bensaid, Khaldoun Bachari, Nadia Taibi, Artur M S SilvaAbstract:The transformations of ( E )-3-[3-(2-hydroxyaryl)-3-oxoprop-1-en-1-yl]Chromones in the presence of methylhydrazine and aromatic bisnucleophiles are described. The reactions generally lead to Chromone ring transformation via pyrone ring-opening and heterocyclization to give novel diazoles and ( Z )-3-aminomethylenechromanones, respectively. Piperazine catalyzes chromanone ring closure of the starting substrate to afford Chromone–chromanone dyads.