- Spectroscopic analysis by NMR, FT-Raman, ATR-FTIR, and UV-Vis, evaluation of antimicrobial activity, and in silico studies of chalcones derived from 2-hydroxyacetophenone
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Six 2’-hydroxychalcones were synthesized and characterized by NMR, FT-Raman, ATR-FTIR, and UV-Vis. These chalcones alone and in combination with the ciprofloxacin, penicillin, and erythromycin antibiotics were tested against multiresistant strains of Staphylococcus aureus. It was also verified by in vitro and in silico studeis the capacity of these chalcones to inhibit the NorA efflux pump. The MICs values of ciprofloxacin were reduced in the presence of all tested chalcones. For norfloxacin antibiotic, the chalcones A1, A4, A5 and A6 promoted the reduced in the MIC values. The A2 chalcone was the only one to reduce the MIC values when associated with penicillin. Any chalcones were not able to reduce MIC values when associated with erythromycin. These results indicate that the synergistic effects demonstrated for the synthesized chalcones were influenced by the introduction of a furanic ring (A1), a chlorine atom and a methoxy group at the C4 position (A2 and A4), a second double bond (A5), and a fluorine atom at the C2 position (A6). The ADMET analysis predicts that the chalcones A2, A3, A5 and A6 have easier cell permeation. The nucleophilic region makes the A5 chalcone capable of covalently bonding with plasma proteins, and the presence of oxygenated aromatic substitutions makes the chalcones A1 and A4 more water-soluble and consequently easier to excrete. On the other hand, the substitution of the methoxy group of the A4 chalcone makes it more susceptible to O-demethylation reactions by the CYP3A4 isoenzyme. The molecular docking revealed that all six chalcones could hinder the binding of norfloxacin to the NorA efflux pump.
- Xavier, Jayze da Cunha,de Almeida-Neto, Francisco W.Q.,Rocha, Janaína E.,Freitas, Thiago S.,Freitas, Priscila R.,de Araújo, Ana C.J.,da Silva, Priscila T.,Nogueira, Carlos E.S.,Bandeira, Paulo N.,Marinho, Márcia M.,Marinho, Emmanuel S.,Kumar, Nitin,Barreto, Ant?nio C.H.,Coutinho, Henrique D.M.,Juli?o, Murilo S.S.,dos Santos, Hélcio S.,Teixeira, Alexandre M.R.
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- Design, synthesis and SARs of novel telomerase inhibitors based on BIBR1532
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Telomerase has become one of the new popular targets for the development of anti-tumor drugs. Based on the structural characteristics of the BIBR1532 which has entered the stage of clinical research, six series total of 64 new compounds with diverse struc
- Chen, Fei Hu,Liu, Chao,Liu, Xin Hua,Sheng, Xiao Bao,Zhou, Hua
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supporting information
(2020/07/21)
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- 2′-Hydroxychalcones as an alternative treatment for trichomoniasis in association with metronidazole
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The treatment for trichomoniasis, based on 5′-nitroimidazol agents, has been presenting failures related to allergic reactions, side effects, and the emergence of resistant isolates. There are no alternative drugs approved for the treatment of these cases; thus, the search for new active molecules is necessary. In this scenario, chalcones have been extensively studied for their promising biological activities. Here, we presented the synthesis of three hydroxychalcones (3a, b, and c), in vitro and in silico analyses against Trichomonas vaginalis. The in vitro biological evaluation showed that hydroxychalcone 3c presented anti-T. vaginalis activity, with complete death in 12?h of incubation at minimum inhibitory concentration (MIC) of 100?μM. 3c showed a dose-dependent cytotoxicity against mammalian VERO cell line, but the association of 3c at 12.5?μM and metronidazole (MTZ) at 40?μM showed 95.31% activity against T. vaginalis trophozoites after 24?h of exposure and did not affect the VERO cell growth, appearing to be a good alternative. In silico analysis by molecular docking showed that 3c could inhibit the activity of TvMGL (methionine gamma-lyase), TvLDH (lactate dehydrogenase), and TvPNP (purine nucleoside phosphorylase) affecting the T. vaginalis survival and also suggesting a different mechanism of action from MTZ. Therefore, these results propose that hydroxychalcones are promising anti-T. vaginalis agents and must be considered for further investigations regarding trichomoniasis treatment.
- Alves, Mirna Samara Dié,Borsuk, Sibele,Casaril, Angela Maria,Ramos, Daniela Fernandes,Savegnago, Lucielli,Sena-Lopes, ?ngela,da Rocha Fonseca, Bárbara,da Silva, Caroline Carapina,das Neves, Raquel Nascimento,de Pereira, Claudio Martin Pereira
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- Small multitarget molecules incorporating the enone moiety
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Chalcones represent a class of small drug/druglike molecules with different and multitarget biological activities. Small multi-target drugs have attracted considerable interest in the last decade due their advantages in the treatment of complex and multifactorial diseases, since “one drug-one target” therapies have failed in many cases to demonstrate clinical efficacy. In this context, we designed and synthesized potential new small multi-target agents with lipoxygenase (LOX), acetyl cholinesterase (AChE) and lipid peroxidation inhibitory activities, as well as antioxidant activity based on 2-/4- hydroxy-chalcones and the bis-etherified bis-chalcone skeleton. Furthermore, the synthesized molecules were evaluated for their cytotoxicity. Simple chalcone b4 presents significant inhibitory activity against the 15-human LOX with an IC50 value 9.5 μM, interesting anti-AChE activity, and anti-lipid peroxidation behavior. Bis-etherified chalcone c12 is the most potent inhibitor of AChE within the bis-etherified bis-chalcones followed by c11. Bis-chalcones c11 and c12 were found to combine anti-LOX, anti-AchE, and anti-lipid peroxidation activities. It seems that the anti-lipid peroxidation activity supports the anti-LOX activity for the significantly active bis-chalcones. Our circular dichroism (CD) study identified two structures capable of interfering with the aggregation process of Aβ. Compounds c2 and c4 display additional protective actions against Alzheimer’s disease (AD) and add to the pleiotropic profile of the chalcone derivatives. Predicted results indicate that the majority of the compounds with the exception of c11 (144 ?) can cross the Blood Brain Barrier (BBB) and act in CNS. The results led us to propose new leads and to conclude that the presence of a double enone group supports better biological activities.
- Liargkova, Thalia,Eleftheriadis, Nikolaos,Dekker, Frank,Voulgari, Efstathia,Avgoustakis, Constantinos,Sagnou, Marina,Mavroidi, Barbara,Pelecanou, Maria,Hadjipavlou-Litina, Dimitra
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- Comparative Photophysical Study of Differently Substituted Cinnamaldehyde-Based Chalcones: From Intramolecular Charge Transfer to Fluorogenic Solvent Selectivity
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We synthesized three cinnamaldehyde-based chalcone derivatives, (2E,4E)-1-(2-hydroxyphenyl)-5-phenylpenta-2,4-dien-1-one (HPD), (2E,4E)-5-(4-(dimethylamino)phenyl)-1-phenylpenta-2,4-dien-1-one (DPPD), and (2E,4E)-5-(4-(dimethylamino)phenyl)-1-(2-hydroxyph
- Bhattacharyya, Arghyadeep,Makhal, Subhash Chandra,Guchhait, Nikhil
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p. 6411 - 6419
(2019/08/26)
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- From Carbamate to Chalcone: Consecutive Anionic Fries Rearrangement, Anionic Si → C Alkyl Rearrangement, and Claisen-Schmidt Condensation
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A highly efficient one-pot procedure was developed for the synthesis of various 2′-hydroxychalcones from phenyl diethylcarbamate, featuring consecutive Snieckus-Fries rearrangement, anionic Si a?' C alkyl rearrangement, and Claisen-Schmidt condensation in a single operation. The applicability of this protocol was demonstrated by the highly efficient synthesis of the anti-inflammatory natural product lonchocarpin. The mechanism insight is also provided.
- Kumar, Singam Naveen,Bavikar, Suhas Ravindra,Pavan Kumar, Chebolu Naga Sesha Sai,Yu, Isaac Furay,Chein, Rong-Jie
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p. 5362 - 5366
(2018/09/12)
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- Diarylpentadienone derivatives (curcumin analogues): Synthesis and anti-inflammatory activity
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A series of new (2E,4E)-1-(substitutedphenyl)-5-(substitutedphenyl)penta-2,4-dien-1-one derivatives were designed and synthesized. Compounds 3i, 3k were determined by X-ray. All of the compounds have been screened for their anti-inflammatory activity characterized by evaluating their inhibition against LPS-induced IL-6 and TNF-α release in cell RAW 264.7 stimulated with LPS. Compound 3i showed the highest anti-inflammatory activity on decreasing IL-6 and TNF-α. The further study showed that title compound 3i inhibited expression of proteins p-p65, iNOS, COX-2 LPS-induced. Immunofluorescence also revealed compound 3i could lightly reduce activation p65 in nuclei. These results indicate that compound 3i anti-inflammatory role may partly due to its inhibitory effect on the NF-κB signaling pathway.
- Wang, Zhi Sen,Chen, Liu Zeng,Liu, Xin Hua,Chen, Fei Hu
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p. 1803 - 1807
(2017/04/04)
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- 1,5-Diphenylpenta-2,4-dien-1-ones as potent and selective monoamine oxidase-B inhibitors
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A series of (2E,4E)-1-(2-hydroxyphenyl)-5-phenylpenta-2,4-dien-1-ones (3a-r) and (2Z,4E)-3-hydroxy-1-(2-hydroxyphenyl)-5-phenylpenta-2,4-dien-1-ones (6a-l) were synthesized and evaluated in vitro as inhibitors of the two human Monoamine oxidase (hMAO) iso
- Desideri, Nicoletta,Fioravanti, Rossella,Proietti Monaco, Luca,Biava, Mariangela,Yanez, Matilde,Ortuso, Francesco,Alcaro, Stefano
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- NHC-catalyzed reaction of enals with hydroxy chalcones: Diastereoselective synthesis of functionalized coumarins
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The N-heterocyclic carbene-catalyzed annulation of enals with 2′-hydroxy chalcones afford cyclopentane-fused coumarin derivatives with an excellent level of diastereocontrol. The reaction tolerates a broad range of functional groups; 25 examples are given, and a preliminary mechanistic investigation is provided.
- Bhunia, Anup,Patra, Atanu,Puranik, Vedavati G.,Biju, Akkattu T.
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supporting information
p. 1756 - 1759
(2013/06/27)
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- Synthesis and evaluation of antioxidant activity of 2-styrylchromones
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Antioxidants are emerging as potential prophylactic and therapeutic agents which scavenge free radicals otherwise reactive oxygen species and prevent the damage caused by them. Free radicals have been associated with pathogenesis of various disorders like
- Pawar, Shrinivas P.,Kondhare, Dasharath D.,Zubaidha
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p. 753 - 757
(2013/04/10)
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- Mosquito larvicidal studies of some chalcone analogues and their derived products: Structure-activity relationship analysis
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A series of chalcone analogues and some of their derivatives were synthesized and subjected to the mosquito larvicidal study. Chalcones having electron releasing group(s) on either ring A or ring B showed high toxicity. Electron withdrawing group(s), especially at ring B, reduced the activity of chalcones. The activity was abruptly decreased due to replacement of ring A by CH3, extension of conjugation or blocking of α,β- unsaturated ketone part of chalcones by derivatization. Quantitative structure-activity relationship (QSAR) studies of these compounds were performed using various spatial, electronic and physicochemical parameters. Genetic Function approximation with linear and spline options was used as the chemometric tool for developing the QSAR models.
- Begum, Naznin A.,Roy, Nayan,Laskar, Rajibul A.,Roy, Kunal
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experimental part
p. 184 - 191
(2012/02/16)
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- Tandem mass spectrometry based investigation of cinnamylideneacetophenone derivatives: Valuable tool for the differentiation of positional isomers
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Cinnamylideneacetophenones have been extensively used as versatile starting materials in numerous different transformations. The structural characterization of this type of compounds is, therefore, of crucial importance since it can give information on th
- Resende, Diana I. S. P.,Silva, Eduarda M. P.,Barros, Cristina,Domingues, M. Rosario M.,Silva, Artur M. S.,Cavaleiro, Jose A. S.
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experimental part
p. 3185 - 3195
(2012/04/10)
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- Synthetic chalcones, flavanones, and flavones as antitumoral agents: Biological evaluation and structure-activity relationships
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A series of synthetic chalcones, flavanones, and flavones has been synthesized and evaluated for antitumor activity against the human kidney carcinoma cells TK-10, human mammary adenocarcinoma cells MCF-7 (estrogen receptor-positive), and human colon adenocarcinoma cells HT-29. The most active series is the chalcone ones with the best results against TK-10 and HT-29 cells. Fourteen out of 53 analyzed compounds resulted very active against at least two of the studied tumoral cells. Alkaline single cell gel electrophoresis, comet assay, was performed as a study of the chromosomal aberrations promoted by the compounds on normal cells. Four active and two inactive chalcones were studied in the comet assay against normal human kidney cells (HK-2). A structure-activity relationship analysis of these compounds was performed and for 4- and 3,4-disubstituted derivatives a quantitative correlation was obtained in the case of anti-HT-29 activity.
- Cabrera, Mauricio,Simoens, Macarena,Falchi, Gabriela,Lavaggi, M. Laura,Piro, Oscar E.,Castellano, Eduardo E.,Vidal, Anabel,Azqueta, Amaia,Monge, Antonio,de Cerain, Adela Lopez,Sagrera, Gabriel,Seoane, Gustavo,Cerecetto, Hugo,Gonzalez, Mercedes
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p. 3356 - 3367
(2008/02/07)
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- Epoxidation of (E,E)-cinnamylideneacetophenones with hydrogen peroxide and iodosylbenzene with salen-MnIII as the catalyst
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(E,E)-Cinnamylideneacetophenones 3a-j were epoxidized under mild conditions with Jacobsen's catalyst 4 and hydrogen peroxide or iodosylbenzene as oxidants. γ,δ-Monoepoxides and a diastereomeric mixture of α,β:γ,δ-diepoxides were obtained in each case, and
- Santos, Clementina M. M.,Silva, Artur M. S.,Cavaleiro, Jose A. S.,Levai, Albert,Patonay, Tamas
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p. 2877 - 2887
(2008/03/13)
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- Biological evaluation of chalcones and analogues as hypolipidemic agents
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In order to evaluate the anti-hyperlipidemic effect of synthetic chalcones and some analogues, nineteen compounds with different substituents in both rings were synthesized and hypolipidemic activities were measured in vivo using Triton WRl339 acute and hypercaloric chronic assays. 4′,4- dichlorochalcone, 3′,4′,4-trichlorochalcone, and 4′-chlorochalcone gave an excellent decrease in serum total cholesterol and triglycerides in the acute assay. These compounds also showed significant anti-lipidemic activity in the chronic assay.
- Santos, Lorena,Pedrosa, Rozangela Curi,Correa, Rogerio,Cechinel Filho, Valdir,Nunes, Ricardo Jose,Yunes, Rosendo Augusto
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p. 541 - 546
(2007/10/03)
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- Novel (E)- and (Z)-2-styrylchromones from (E,E)-2′-hydroxycinnamylideneacetophenones - Xanthones from daylight photooxidative cyclization of (E)-2-styrylchromones
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The oxidative cyclization of (E,E)-2′-hydroxycinnamylideneacetophenones 1a-e, and (E,E)-2′-benzyloxy-6′-hydroxycinnamylideneacetophenones 1i-1 with DMSO/ iodine, gave (E)-2-styrylchromones 3a-e,i-1. However, in the case of (E,E)-γ-alkyl-2′-hydroxycinnamyl
- Silva, Artur M. S.,Pinto, Diana C. G. A.,Tavares, Hilario R.,Cavaleiro, Jose A. S.,Jimeno, M. Luisa,Elguero, Jose
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p. 2031 - 2038
(2007/10/03)
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- Oxidative cyclization of o-hydroxy-ω-cinnamylideneacetophenones to 2-styrylchromones with potassium iodate-dimethyl sulphoxide
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o-Hydroxy-ω-cinnamylideneacetophenones (1) have been found to undergo oxidative cyclization to the corresponding 2-styrylchromones (2) in satisfactory yields by heating them with potassium iodate in dimethyl sulphoxide.
- Singhi, Manasi,Grover, S. K.
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p. 1083 - 1084
(2007/10/02)
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- A modified synthesis of 2-styrylchromones
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2-Hydroxy-ω-cinnamylideneacetophenones (3a-e) have been obtained by condensation of 2-hydroxyacetophenones (1) with cinnamaldehyde (2) in the presence of barium hydroxide.Oxidative cyclisation of the compounds 3a-e with iodine in dimethyl sulphoxide provi
- Makrandi, J. K.,Seema
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p. 788 - 789
(2007/10/02)
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- Photochemical Cyclization of 2'-Hydroxychalcones
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A series of 4-substituted 2'-hydroxychalcones underwent photocyclization to give the corresponding flavones selectively, but in low quantum yields, on visible irradiation in polar aprotic solvents.Hydroxylic solvents, which disturbed the formation of a cyclic intramolecular hydrogen bond, strongly retarded the photoreaction, while neither triplet quenchers nor free radical inhibitors affected the reaction.The quantum yields were independent of the light intensity, implying a one-photon process, but strongly depended on the wavelength of irradiation.Mechanisms were proposed assuming ?, ?* excited states and Weller's postulate of a dynamic equilibrium in a proton-transfer double-minimum potential.
- Matsushima, Ryoka,Kageyama, Hiroyuki
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p. 743 - 748
(2007/10/02)
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- STUDIES ON THE CONDENSATION PRODUCTS OF SOME α, β -UNSATURATED CARBONYL COMPOUNDS WITH 4-HYDROXYCOUMARIN
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The base catalysed condensation products of mesityl oxide and benzalacetone with 4-hydroxycoumarin have been studied.The reported structures (III) and (IX) of two condesation products are revised as (V) and (X) respectively.Chemicxal transformations of (V
- Talapatra, Sunil K.,Chakrabarti, Ramaprasad,Mukhopadhyay, Pradyot K.,Das, Prabir K.,Talapatra, Bani
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p. 519 - 526
(2007/10/02)
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