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.

Two new chalcones from Fordia cauliflora

Two new chalcones,β,2′,4′,5′-tetramethoxychalcone 1,andβ,2′,5′-trimethoxyfurano[4″,5″：3′,4′]-chalcone 2 were obtainedfrom an ethyl acetate-soluble fraction of ethanol extract of the stem of Fordia cauliflora.Their chemical structures were determinedby analysis of spectroscopic evidences.

A Facile Synthetic Approach to Two Chalcones

A facile synthetic route for two chalcone analogues was developed. The key step was selective deprotection of MOM in aryl methyl ether 6 by silica gel.

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.

An efficient synthesis of pyrazole chalcones under solvent free conditions at room temperature

An easy, safe, solvent free and effective method for the synthesis of pyrazole-substituted chalcones has been achieved by grinding pyrazole aldehydes and acetophenones in the presence of activated barium hydroxide （C-200） in high yield within short span of time. All reactions were carried out just by grinding the two reactants in the presence of activated barium hydroxide （C-200）. Results are also compared with sodium hydroxide and potassium hydroxide.

Direct Asymmetric Michael Additions of Ketones to Nitroolefins and Chalcones Catalyzed by a Chiral C2-Symmetric Pyrrolidine-based Tetraamine

C2-Symmetric pyrrolidine-based tetraamine, available from commercially starting materials, showed good cata- lytic activity for asymmetric Michael additions of ketones to nitroalkenes especially to chalcones. The reactions proceeded to give the corresponding products in good yields and in a highly selective manner.

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。

Cloning of Tap Ⅱ Chalcone Isomerases(CHI1 A) Gene and Construction of Lactococcus Lactis Expression Vector

[Objective]The aim was to clone TapⅡchalcone isomerases（CHI1 A） from soybean specially and construct expression vector of PNZ8149-CHI1 A,and then transform it into Lactococcus Lactis NICE systers.[Method]Chalcone isomerases（CHI1 A） was cloned by RTPCR method,and it was sequenced after cloning into pMD18-T vectors,and recombined to expression vector PNZ8149-CHI1 A,then it was transformed into Lactococcus Lactis NZ3900[Result]The sequencing results indicated that the cloned fragment of CHI1 A contained 670 nucleotides,and shared a sequence homology of 92% with that from Genbank accession number AF595413（CHI1 A）.CHI1 A was transformed into NICE expression system successfully by identification of PCR and digestion.[Conclusion]The foundation of using the microorganism fermentation method to produce flavonoids was laid by construction of efficient induction expression vector with chalcone isomerases CHI1 A.

Molecular Composition and Evolution of the Chalcone Synthase (CHS) Gene Family in Five Species of Camellia (Theaceae)

The molecular composition and evolution of the chalcone synthase (CHS) gene family from five species in Camellia (Theaceae) are explored in this study. Sixteen CHS exon 2 from four Camellia species were amplified from total DNA by PCR method. Three sequences of the fifth species in Camellia and two sequences of Glycine max as the designated outgroups were obtained from GenBank. Our results indicated that CHS gene family in Camellia was differentiated to three subfamilies (A, B, C) during the evolutionary history with six groups (A1, A2, A3, BI, B2, C). Among them, only group A2 was possessed by all five species in this study. However, the other five groups were detected only in some species of the plants studied. All members of CHS gene family in this study had high sequence similarity, more than 90% among the members in the same subfamily and more than 78% among different subfamilies at nucleotide level., According to the estimated components of amino acids, the function of CHS genes in Camellia had been diverged. The nucleotide substitutions of the different groups were not identical. Based on phylogenetic analyse inferred from sequences of CHS genes and their deduced amino acid sequences, we concluded that the CHS genes with new function in this genus were evolved either by mutations on several important sites or by accumulation of the mutations after the gene duplication. A further analysis showed that the diversification of CHS genes in Camellia still occurred recently, and the evolutionary models were different to some extant among different species. So we assumed that the different evolutionary models resulted from the impacts of variable environmental elements after the events of speciation.

Synthesis of a New Series of Chalcone Derivatives and Their Antifungal Activities

To study the antifungal effect of chalcone derivatives. Methods Sixteenchalcone derivatives were synthesized and confirmed by ~1H NMR and IR spectra, and tested forantifungal activity against four common pathogenic fungi. Their structure-activity relationship isdiscussed. Results Among 16 title compounds, there were 5 new compounds, which have not beenreported before. The preliminary antifungal test showed that all title compounds exhibitedantifungal activities to a certain extent. The activity of compound 8 against Trichophyton rubrumhad a potency equal to that of fluconazole, with a MIC of 4 μg·mL^(-1) . Conclusion Sixteenchalcones were prepared and their antifungal activities against four common pathogenic fungi invitro were examined. Some of them exhibited antifungal activities to a certain extent.