A Solid Phase Synthesis of Chalcones by Claisen-Schmidt Condensations

In order to accelerate the development of relatively inexpensive antimalarials that are effective against chloroquine-resistant strains of Plasmodium falciparum, a methodology for the solid phase synthesis of chalcone (1, 3-diphenyl-2-propen-1-one) analogues in reasonably high yields has been developed.

(E)-2-Benzylidenecycloalkanones XII.*Kinetic Measurement of Bovine and Human Serum Albumine Interaction with Selected Chalcones and Their Cyclic Chalcone Analogues by UV Spectrophotometry

UV-VIS spectroscopic investigations of interaction of bovine and human serum albumin with selected chalcones (1) and their cyclic chalcone analogues: (E)-2-(4’-X-benzylidene-1-tetralones (3), benzosuberones (4) with dimethylamino and methoxy substituents and (E)-2-(2’,4’-dimethox- ybenzylidene)-1-indanone (2) were performed in polar respiration medium. Absorption maxima of the tested compounds were investigated in the presence of bovine and human serum albumin at the 0, 10, 30 and 60 minute timepoints of the interaction. The absorbance of all studied compounds in the presence of proteins decreased after one hour of the reaction. Molecule 4a showed the strongest and fastest kinet initial interaction with both albumins.

Antioxidant and Cytotoxicity Potential of Six Synthesized Chalcones

Background: Chalcones are open-chain flavonoids which display a large number of pharmacological activities such as cytotoxic, anti-inflammatory including antioxidant. The objective of this study was to assess antioxidant and cytotoxic activity of six synthesized chalcones. Methodology: For the current experiments, 1,3-diphenylpropenone (compound R) was used as molecular model to synthetize six compounds, namely three benzyl-benzimidazolyl-chalcones (U1, U2, WAC1) and three imidazopyridinyl-chalcones (V1, V2, V3). All the compounds were evaluated for their ability to scavenge the stable free ABTS.+ radical cation, according to the method develop by Choong et al. In addition, the cytotoxicity test described by Price et al., was performed using healthy human cell line, then in human malignant cell lines (HEP-2, A549). Results: All synthesized chalcones reduced the ABTS.+ radical cation. Indeed, benzyl benzimidazolyl compounds WAC1, U1, U2, by developing respectively 39.61%, 66.09%, and 84.20% percentages of reduction, showed an antioxidant effect 6, 11 and 14 times greater than the compound R (6.14%). As a result, imidazopyridinyl-chalcones compounds, namely V1, V2 and V3 reduced the ABTS.+ radical cation at 91.62%, 99.84% and 97.45% respectively, being 15 and 16 times more active than the compound R. About cytotoxicity, V2 inhibited not significantly HEP-2 malignant cells growth at 48.64%, compared to the standard product, i.e. doxorubicin that inhibited the growth of the same cells at 42.37%. WAC1 inhibited significantly the growth of A549 malignant cells at 89.53%, more than doxorubicin which percentage of growth inhibition was 71.58%. Conclusion: The presence of the α, β-unsaturated carbonyl system (or 1,3-diphenylpropenone) along with a benzimidazole or imidazopyridine heterocyclic ring is likely to contribute to both cytotoxic and antioxidant activities of these compounds.

Investigation of Interaction of Some Chalcones and Cyclic Chalcone Analogues with Outer Mitochondrial Membrane by UV-VIS and Fluorescence Spectroscopy

Interaction of the synthetic chalcones (1b,1c) and their cyclic analogues (2b,2c) with bovine (BSA) and human serum albumin (HSA) as well as with rat liver mitochondria (RLM) was studied by fluorescence spectroscopy. The maxima of emission fluorescence spectra were changed only in the case of 2b and 2c during interaction with BSA, HSA as well as mitochondrial outer membrane showing a slight hypsochromic shift and decrease of fluorescence. Interaction of the methoxy-(1b,2b) and the dimethylamino-substituted (1c,2c) compounds with outer mitochondrial membrane were studied by fluorescence polarization. Fluorescence polarization of 1b in the presence of the two proteins and mitochondria was found to be unchanged. Under similar conditions (2b,1c,2c) showed continuously increasing fluorescence polarization signal during the 30 minute period of investigations. Since fluorescence polarization supposes that as a result of binding these substances to proteins and lipids. Compound 2c displayed a continuous increase of fluorescence polarization signal in the presence of proteins (BSA, HSA), yeast cytoplasm (YC) and mitochondria (YM and RLM). This compound displayed a significant cytotoxic effect. This pattern of interaction with proteins might be one of the contributing vectors of the observed cytotoxicity against several human carcinoma cell lines.

Evaluation of the Antibacterial and Antifungal Capacity of Nanoemulsions Loaded with Synthetic Chalcone Derivatives Di-Benzyl Cinnamaldehyde and Benzyl 4-Aminochalcone

With the increase in antimicrobial resistance,it has become necessary to explore alternative approaches for combating and preventing diseases.DB-cinnamaldehyde(CNM)and Benzyl4-amino(B4AM)are bioactive compounds derived from chalcones but with restricted solubility in aqueous media.Nanoemulsions can enhance the solubility of compounds and can be a promising alternative in the development of novel antimicrobials,with reduced side effects and prolonged release.The objective of this study was to evaluate the stability of oil-in-water nanoemulsions loaded with two distinct types of chalcones at two different dosages,to propose a stable formulation with antimicrobial properties.Results showed that nanoemulsions presented high encapsulation efficiency,low polydispersity index(PDI)and particle size below 200 nm,indicating that emulsification was a suitable method for nanoemulsion preparation.Nanoemulsions with higher dosages exhibited significant antimicrobial effects when compared to free chalcones and positive controls.Notably,B4AM nanoemulsions at higher dosages showed expressive activity against Salmonella minnesota,with a 420%greater inhibitory response compared to the free form and showing equivalence to the positive control.CNM nanoemulsions showed excellent inhibitory activity at the highest dosage,equivalent to the positive control against S.minnesota and Staphylococcus aureus.The greater number of conjugated bonds in CNM increased the antimicrobial activity in comparison with B4AM,and the formation of nanometric domains enhanced the bioavailability,being a promising alternative for antimicrobial applications.

Ag_(2)CO_(3)-catalyzed efficient synthesis of internal or terminal propargylicamines and chalcones via A^(3)-coupling under solvent-free condition

Several simple, fast and practical protocols have been developed to synthesize internal or terminal propargylamines and chalcones via A^(3)-coupling reaction of aldehydes, amines, and alkynes catalyzed by an easily available catalyst Ag_(2)CO_(3)under solvent-free condition. The reaction proceeded smoothly to deliver various products in good-to-excellent yields with good functional group tolerance. Gram-scale preparation, bioactive molecule synthesis and asymmetric substrates have been demonstrated. Furthermore,plausible mechanisms for the synthesis of different products have been proposed.

A Simple Access to Chalcones via Modified Mukaiyama Aldol Condensation Promoted by SmI_3/TMSCl

Promoted by SmI3, acetophenones and benzaldehydes can undergo the Mukaiyama type aldol condensation in the presence of TMSCl to form chalcones in good yields.

Synthesis and pharmacological properties of naturally occurring prenylated and pyranochalcones as potent anti-inflammatory agents

An efficient approach has been developed for the synthesis of naturally occurring prenylated chalcones viz. kanzonol C （1）, stipulin （2）, crotaorixin （3）, medicagenin （4）, licoagrochalcone A （5） and abyssinone D （6） along with the pyranochalcones paratocarpin C （7）, anthyllisone （8） and 3-O-methylabyssinone A （9）. The key step of the synthesis is a Claisen-Schmidt condensation. Subsequently, their anti-inflammatory effects were investigated in lipopolysaccharides （LPSs）-induced RAW-264.7 macrophages. Of the synthesized chalcones, compounds 5 （IC50= 10.41 μmol[L）, 6 （IC50= 9.65 μmol/L） and 8 （IC50= 15.34 μmol/L） show remarkable activity with no cytotoxicity. Compound 9 （IC50 = 4.5 μmol/L） exhibits maximum （83.6%） nitric oxide （NO） inhibition, but shows slight cytotoxicity. The results reveal that the chalcones bearing the prenyl group at 3- and/or 5-position on ring A （acetophenone moiety）, i.e., 1-4 and 7 show weak, or no inhibition activity, whereas chalcones having the prenyl group only on ring B （aldehyde part）, i.e., 5, 6 and 8 show significant activity on the production of inflammatory mediated NO with no cytotoxicity.

Chemical modification of acetaminophen：PASS assisted in vivo antiinflammatory activity of chalcones,flavanones and Schiff bases

In the present study,synthetic chalcones,flavanones and Schiff bases were prepared starting from paraceamol,and evaluated their anticipated anti-inflammatory activity.Chalcones were synthesized by reacting 3-acetyl-4-hydroxy acetanilide and aromatic aldehydes in alcoholic potassium hydroxide(KOH) solution under Claisen-Schmidt condensation conditions.The chalcones were cyclized in the presence of piperidine in isoamyl alcohol to obtain flavonone derivatives.Schiff bases were synthesized by condensing 3-acetyl-4-hydroxy anilines with aromatic aldehydes in the presence of HCl.These Schiff bases were further reacted with other aromatic aldehydes in alcoholic KOH solution.PASS cheminformatics software was used to predict the anti-inflammatory activity of synthesized compounds.PASS software predicted that chalcone-based Schiff bases 6a–d contained structural features that can exhibit anti-inflammatory activity.All the prepared derivatives of acetaminophen exhibited moderate to excellent in vivo anti-inflammatory activity in carrageenan-induced edema in rat paw.All the Schiff bases coupled chalcones showed good anti-inflammatory activity compared with the reference drug,diclofenac.Further evaluation of their therapeutic potential and safety profile is required in the future study.

Oxidant Promoted 1,3-Dipolar Cycloaddition of Pyridinium Ylides to Chalcones for Preparation of 1-Benzoyl-2-arylindolizines

The derivatives of 1-benzoyl-2-arylindolizine were prepared in moderate yields of 41%-78% by CrO3/Et3N promoted 1,3-dipolar cycloaddition of pyridinium N-ylides and chalcones. Under the same conditions, CrO3/Et3N promoted 1,3-dipolar cycloaddition of isoquinolinium N-ylides and chalcones provided the corresponding 1-benzoyl-2-arylpyrrolo[2,1-a]isoquinolines in 45 %-61% yields.

Design,synthesis and bioactivity of chalcones and its analogues

The Vernohia anthelmintica L.＇s extract is one of the most popular Uygur medicines used for vitiligo. It is believed that the chalcone compounds of the plant play an important role in the treatment since they may activate tyrosinase and improve melanin production. In this study, twenty-one chalcones and nine analogues were synthesized in view of three different components of chalcone（A, B ring and a,b-unsaturated carbonyl）. After biological evaluation of their activity on tyrosinase in cell-free systems,the result showed that most compounds（except polyhydroxy chalcones） possess activator effect on the tyrosinase, especially for 13a–15a, 20 a and 1b, which bearing a comparable activity to the positive control8-MOP. SAR of these tyrosinase activator was summed up for the first time as well. Finally, compound 13 a was found to increase melanin contents and tyrosinase activity 1.75 and 1.3 fold, respectively, compared with that of untreated murine B16 cells at the concentration of 40 mg/m L.

New Convenient Synthesis of 8-C-Methylated Homoisoflavones and Analysis of Their Structure by NMR and Tandem Mass Spectrometry

Homoisoflavonoids are in the subclass of the larger family of flavonoids having one more alkyl carbon than flavonoids. Among them, 8-C-Methylated homoisoflavones have not been extensively studied for synthesis and biological evaluation. Author’s current objective is to synthesize 8-C-Methylated homoisoflavones by the reaction of 3-C-methylated dihydrochalcones with N,N’-dimethyl (chloromethylene) ammonium chloride generated in situ from DMF and PCl5 for one carbon extension at about room temperature. The 3-C-methylated dihydrochalcones were synthesized by the reduction of 3-C-methylated chalcones, which were prepared from 3-C-methylated acetophenones and aromatic aldehydes in the presence of base. All the synthesized novel homoisoflavones’s structures were characterized by NMR and Tandem Mass Spectrometry.

茶树CHS基因结构及编码区单核苷酸多态性分析

【目的】通过试验获得茶树CHS基因(CsCHS)gDNA序列,以进一步确定CsCHS基因结构;研究CsCHS编码区单核苷酸多态性,并结合茶树多酚含量进行关联分析,寻找基因中可能存在的与茶多酚含量存在显著或极显著相关关系的SNP位点。【方法】根据NCBI数据库中已有CsCHS序列设计特异性引物,再分别以基因组DNA和cDNA为模板进行PCR扩增,经克隆、测序获得CsCHS1、CsCHS2、CsCHS3三个基因的gDNA和cDNA全长序列,通过序列比对方法确定CsCHS结构。利用Compute pI/Mw、SOPMA等软件对所得序列进行生物信息学分析,预测和比较CsCHS1、CsCHS2和CsCHS3三者蛋白质结构。以茶多酚含量差异较大的57份茶树品种为材料,分别以57份材料的cDNA为模板,用特异性引物进行PCR扩增,然后利用PCR产物直接测序法筛查CsCHS编码区序列的单核苷酸多态性。结合CsCHS编码区序列单核苷酸多态性和57份材料多酚含量,利用软件TASSEL进行关联分析,筛选基因中可能与茶多酚含量存在显著或极显著相关关系的SNP位点。【结果】试验获得CsCHS1、CsCHS2和CsCHS3的cDNA序列长度分别为1 277、1 320和1 242 bp,各自均包含一个长度为1 170 bp的开放阅读框;CsCHS1、CsCHS2和CsCHS3的gDNA序列长度分别为1 600、1 330和1 607 bp。通过gDNA序列和cDAN序列比对,结合真核生物内含子GT-AG法则,确定CsCHS1、CsCHS3分别包含2个外显子和1个内含子,内含子大小分别为323和356 bp,CsCHS2可能没有内含子。根据CsCHS1、CsCHS2和CsCHS3 cDNA序列推导三者对应氨基酸序列,比较三条氨基酸序列发现三者氨基酸同源性较高,达到92.6%—95.4%,CHS蛋白亚家族中的特征性保守位点在这三条序列中都能找到,生物信息学分析结果显示CsCHS1、CsCHS2和CsCHS3三者蛋白质结构高度相似。CsCHS1编码区序列中共发现71个SNP位点,SNP出现频率为1SNP/16.48 bp,无Indel,基因核苷酸多样性(π)值为0.01088;CsCHS2编码区序列中共发现55个SNP位点,SNP出现频率分别为1SNP/21.27 bp,CsCHS2核苷酸多样性(π)值(0.00530)明显低于CsCHS1;因扩增CsCHS3 cDNA序列的PCR反应成功率低,未对该基因遗传多样性进行分析。通过关联分析分别从CsCHS1和CsCHS2中找到2个和4个与茶叶多酚含量相关的SNP位点。【结论】CsCHS1和CsCHS3属于保守型CHS基因,且CsCHS1、CsCHS2和CsCHS3蛋白质结构高度相似,推测三者可能在茶树的不同部位或不同生长阶段发挥类似作用;CsCHS1和CsCHS2活跃,二者编码区内可能存在突变热点区。

Synthesis and Trypanocidal Evaluation of Some Novel 2-(Substituted Benzylidene)-5, 7-Dibromo-6-Hydroxy-1-Benzofuran-3(2<i>H</i>)-Ones

Substituted 2-benzylidene-1-benzofuran-3-ones are commonly known as aurones. This class of bioactive heterocycles belongs to flavonoid family. The article intends to put forth the rational design and synthesis of a new series of aurones using 3’,5’-dibromo-2’,4’-dihydroxychalcones and copper bromide in presence of DMF-water mixture (8:2, v/v) for the first time. Preliminary bioassay shows that most of compounds have good trypanocidal activity against Trypanosoma cruzi at 10 μg/mL. Few compounds are equally potent to the standard drugs Benznidazole and Nifurtimox. The structures of the newly synthesized products 2a-n were established by elemental analysis, FTIR, 1H NMR, 13C NMR and mass spectroscopic studies.

Synthesis, Spectroscopic Investigations, Quantum Chemical Studies (<i>Ab-initio</i>&DFT) and Antimicrobial Activities of 3-(3-Chloro-4,5-dimethoxy-phenyl)-1-(4, 5-dimethoxy-2-methyl-Phenyl) prop-2-en-1-one

The chalcones (1,3-diaryl-2-propenones) and their derivatives are important intermediates in organic synthesis and have widespread applications in medicinal industry. The title choloro chalcone derivative, 3-(3-chloro-4,5-dimethoxyphenyl)-1-(4,5-dimethoxy-2-methyl phenyl) prop-2-en-1-one, has been synthesized. It is characterized by FTIR, 1H NMR, 13C NMR and single crystal X-ray diffraction. Title compound crystallizes in monoclinic space group C2/c with a = 23.540(11) ?, b = 9.738(4) ?, c = 17.305(7) ?, β = 106.37 (3)°, V = 3806(3) ?3 and Z = 8. The mean plane of the two substituted benzene rings are twisted by 66.29 (12)° with respect to each other. Ab-initio and density functional Theory (DFT) calculations have been carried out for the title molecule using RHF/6-311G and B3LYP/6-311G basis set respectively. The calculated results show that the predicted geometry can well reproduce structural parameters. In addition, frontier molecular orbitals and Mullikan charge distributions are carried out by using RHF and B3LYP methods. The calculated HOMO and LUMO energies show that charge transfer occurs in the molecule. Numbers of weak but significant interactions like C-H···O, C-H···π and π-π are involved in the stability of the structure. The weak π-π stacked interaction involves the centroids of the methyl phenyl rings with Cg-Cg separation distance of 3.857(2) ?. Synthesized compound has been screened for its antimicrobial activity against different panels of organisms.

Effect of Substituent Position on the Properties of Chalcone Isomer Single Crystals

This paper summarizes the synthesis, growth and the effect of the position of the substituent in the thienyl ring and also the properties of the grown chalcone crystals, 2-CTP and 3-CTP. The formation of compound is confirmed by the re- corded H1NMR spectra. A FT-IR spectrum confirms the presence of all functional groups in both of the crystals. Single crystal XRD reports that even though these two compounds crystallize in monoclinic crystal system, 2-CTP has centro- symmetric P21/c space group and 3-CTP has non-centrosymmetric space group P21. Thermal properties of grown crys- tals analyzed by TG/DTA study explain that the 3-CTP compound is slightly more stable than 2-CTP. The transparency of these isomers in the vis-IR region has been studied. Second and third order nonlinear optical properties of 3-CTP and 2-CTP crystals have been investigated by powder SHG and Z-scan technique respectively.

Synthesis and Crystal Structure of 9-[3-Oxo-1-(4-bromopheny)-3-phenypropyl] fluorine

A novel compound of 9-[3-oxo-1-（4-bromopheny）-3-phenypropyl]fluorine （3） was synthesized via nucleophilic addition reaction under solvent-free condition. Its structure was determined by IR, 1H NMR, MS, elemental analysis and X-ray diffraction. The crystal of the new compound is of triclinic system, space group P-1 with a=9.7919（16）, b=11.0932（18）, c=11.2534（19） , α=76.927（3）, β=67.452（3）, γ=84.895（3）°, V=1099.7（3） 3, Z=2, Dc=1.369 g/cm3, μ=1.886 mm-1, F（000）=464, R=0.0586 and wR=0.1562 for 3145 observed reflections with Ⅰ 2σ（Ⅰ）. π-π Stacking interactions contribute to the stability of the structure.

Guanidinium Lactate Ionic Liquid: An Efficient and Recycling Catalyst for Michael Addition Reaction

A facile and efficient 1, 4-conjungate addition（Michael addition） reaction of active methylene compounds to aft-unsaturated compounds, catalyzed by guanidinium lactate ionic liquid（IL9）, has been developed. A range of chalcones and nitroalkenes together with active methylene compounds have been converted smoothly to the corresponding products in high yields.

Chalcone analogue as potent anti-malarial compounds against Plasmodium falciparum:Synthesis,biological evaluation,and docking simulation study

Objective: To investigate in vitro antimalarial activity of chalcone derivative compounds against Plasmodum falciparum 3D7(Pf3D7) strain and in silico antimalarial activity.Methods: Synthesis of the chalcone derivatives was conducted via Claisen-Schmidt method using NaOH 60% base as catalyst. An in vitro antimalarial activity assay was carried out according to the Rieckmann method against the chloroquine-sensitive Pf3D7 strain. Molecular docking studies of the prepared compounds were performed using Discovery Studio 3.1(Accelrys, Inc., San Diego, USA) software to dihydrofolate reductases-thymidylate synthase(PfDHFR-TS) protein with Protein Data Bank ID of 1J3I.pdb(sensitive-protein) and ID: 4DP3.pdb(resistance-protein).Results: This work has successfully synthesized seven chalcone derivatives with a great antimalarial activity. It has been revealed that allyloxy, hydroxy and alkoxy functional groups could increase the antimalarial activity of the chalcone derivatives. The best antimalarial activity of the prepared compounds was possessed by 3b with an IC_(50) value of 0.59 μM and categorized as an excellent antiplasmodial. Molecular docking studies of 3b showed binding interaction with the amino acid residues such as Ala16. Ile 164. Phe58.Tyr170 of the 1J3I.pdb protein and also Ala16, Phe58, Ile 112, Met55 of the 4DP3.pdb protein.Conclusions: An in vitro antimalarial assay of the prepared chalcone derivative(3a-g)showed an excellent and good antiplasmodial activity against the chloroquine-sensitive Pf3D7 strain. In silico antimalarial studies revealed that 3a-g made binding interaction with both sensitive-protein(IJ3I.pdb) and resistance-protein(4DP3.pdb), which means that they were both active against chloroquine-sensitive and resistant plasmodium strain.