Heterocyclic Analogs Of Chalcone Research Articles

Synthesis and cytotoxic activity of novel chalcone analogues with pyridine-2,4(1<i>H</i>,3<i>H</i>)-dione fragment

New heterocyclic chalcone analogues with pyridine-2,4(1 Н ,3 Н )-dione fragment were synthesized by the condensation reaction of 3-acetylpyridine-2,4(1 H ,3 H )-diones with different aromatic aldehydes in pyridine in the presence of a catalytic amount of piperidine and acetic acid. Structures of the synthesized compounds were confirmed by of IR, 1H, 13C NMR spectroscopy methods and two-dimensional NMR spectroscopy methods and elemental analysis data. Cytotoxic activity of the series of obtained compounds was investigated in vitro against human cell lines of breast cancer (MCF-7) and liver cancer (Hep G2).

ChemInform Abstract: A Facile Access to Novel Heterocyclic Analogues of Chalcone from Newly Synthesized Ketone Containing Isoxazole and a Benzoxazinone Ring.

AbstractCompounds (IIIa‐c,e) and (Va,c,e) show antibacterial activity.

A facile access to novel heterocyclic analogues of chalcone from newly synthesized ketone containing isoxazole and a benzoxazinone ring

A series of novel heterocyclic analogs of chalcone containing isoxazole and benzoxazinone ring as a prime motif was rationally designed and synthesized. There is nothing in the literature about such α,β-unsaturated ketones.

Monoamine oxidase inhibitory activities of heterocyclic chalcones.

Studies have shown that natural and synthetic chalcones (1,3-diphenyl-2-propen-1-ones) possess monoamine oxidase (MAO) inhibition activities. Of particular importance to the present study is a report that a series of furanochalcones acts as MAO-B selective inhibitors. Since the effect of heterocyclic substitution, other than furan (and more recently thiophene, piperidine and quinoline) on the MAO inhibitory properties of the chalcone scaffold remains unexplored, the aim of this study was to synthesise and evaluate further heterocyclic chalcone analogues as inhibitors of the human MAOs. For this purpose, heterocyclic chalcone analogues that incorporate pyrrole, 5-methylthiophene, 5-chlorothiophene and 6-methoxypyridine substitution were examined. Seven of the nine synthesised compounds exhibited IC50 values <1 μM for the inhibition of MAO-B, with all compounds exhibiting higher affinities for MAO-B compared to the MAO-A isoform. The most potent MAO-B inhibitor (4h) displays an IC50 value of 0.067 μM while the most potent MAO-A inhibitor (4e) exhibits an IC50 value of 3.81 μM. It was further established that selected heterocyclic chalcones are reversible and competitive MAO inhibitors. 4h, however, may exhibit tight-binding to MAO-B, a property linked to its thiophene moiety. We conclude that high potency chalcones such as 4h represent suitable leads for the development of MAO-B inhibitors for the treatment of Parkinson's disease and possibly other neurodegenerative disorders.

Structural Correlation of Some Heterocyclic Chalcone Analogues and Evaluation of Their Antioxidant Potential

A series of six novel heterocyclic chalcone analogues 4(a–f) has been synthesized by condensing 2-acetyl-5-chlorothiophene with benzaldehyde derivatives in methanol at room temperature using a catalytic amount of sodium hydroxide. The newly synthesized compounds are characterized by IR, mass spectra, elemental analysis and melting point. Subsequently; the structures of these compounds were determined using single crystal X-ray diffraction. All the synthesized compounds were screened for their antioxidant potential by employing various in vitro models such as DPPH free radical scavenging assay, ABTS radical scavenging assay, ferric reducing antioxidant power and cupric ion reducing antioxidant capacity. Results reflect the structural impact on the antioxidant ability of the compounds. The IC50 values illustrate the mild to good antioxidant activities of the reported compounds. Among them, 4f with a p-methoxy substituent was found to be more potent as antioxidant agent.

Heterocyclic Chalcone Analogues as Potential Anticancer Agents

Chalcones, aromatic ketones and enones acting as the precursor for flavonoids such as Quercetin, are known for their anticancer effects. Although, parent chalcones consist of two aromatic rings joined by a three-carbon α,β-unsaturated carbonyl system, various synthetic compounds possessing heterocyclic rings like pyrazole, indole etc. are well known and proved to be effective anticancer agents. In addition to their use as anticancer agents in cancer cell lines, heterocyclic analogues are reported to be effective even against resistant cell lines. In this connection, we hereby highlight the potential of various heterocyclic chalcone analogues as anticancer agents with a brief summary about therapeutic potential of chalcones, mechanism of anticancer action of various chalcone analogues, and current and future prospects related to the chalcones-derived anticancer research. Furthermore, some key points regarding chalcone analogues have been reviewed by analyzing their medicinal properties.

Heterocyclic Chalcone Analogues as Potential Anticancer Agents

Chalcones, aromatic ketones and enones acting as the precursor for flavonoids such as Quercetin, are known for their anticancer effects. Although, parent chalcones consist of two aromatic rings joined by a three-carbon α,β-unsaturated carbonyl system, various synthetic compounds possessing heterocyclic rings like pyrazole, indole etc. are well known and proved to be effective anticancer agents. In addition to their use as anticancer agents in cancer cell lines, heterocyclic analogues are reported to be effective even against resistant cell lines. In this connection, we hereby highlight the potential of various heterocyclic chalcone analogues as anticancer agents with a brief summary about therapeutic potential of chalcones, mechanism of anticancer action of various chalcone analogues, and current and future prospects related to the chalcones-derived anticancer research. Furthermore, some key points regarding chalcone analogues have been reviewed by analyzing their medicinal properties.

Synthesis and Antibacterial Activity of Some Heterocyclic Chalcone Analogues Alone and in Combination with Antibiotics

A series of simple heterocyclic chalcone analogues have been synthesized by Claisen Schmidt condensation reactions between substituted benzaldehydes and heteroaryl methyl ketones and evaluated for their antibacterial activity. The structures of the synthesized chalcones were established by IR and 1H-NMR analysis. The biological data shows that compounds p5, f6 and t5 had strong activities against both susceptible and resistant Staphylococcus aureus strains, but not activity against a vancomycin and methicillin resistant Staphylococcus aureus isolated from a human sample. The structure and activity relationships confirmed that compounds f5, f6 and t5 are potential candidates for future drug discovery and development.

Electronic structure-activity relationship for derivatives of propenone. Communication II. 2-cinnamoylbenzimidazoles and 2-(β-benzoylvinyl)-1-methylbenzimidazoles

Our systematic investigations of some regularities of the electronic structure-activity relationship (ESAR) in a series of chalcone derivatives and the corresponding heterocyclic analogs substantiated the structural characteristics that determine the antioxidant, antiallergic, antiinflammatory, and other types of activity [1, 2]. In earlier communications we described the results of antiallergic activity studies [1] and the analysis of ESAR for derivatives of 4-carboxyvinylenechalcones and 3-einnamoylcoumarins [3]. As a continuation of these studies, we considered it reasonable to obtain heterocyclic analogs of chalcone, in which one of the aromatic rings was replaced by the benzimidazole fragment. Benzimidazole derivatives are known to process more than 25 types of pharmacological action, including antiallergic [4] and immunomodulating activity (dibazole). We synthesized two types of benzimidazole analogs, 2cinnamoylbenzimidazoles and 2-(13-benzoylvinyl)-l-methylbenzimidazoles (see Table I). Compounds I a n were synthesized by condensation of 2-acetylbenzimidazole with aromatic aldehydes in the presence of a basic or acidic catalyst; compounds I I a n were synthesized by the reaction of 2-formyl-l-methylbenzimidazole with corresponding acetophenones. Biological testing of the compounds obtained revealed pronounced antiallergic and sedative activities (AA and SA, respectively) as well as moderate hypotensive and antihemorrhagic activities. The outlined conclusions [3] about the decisive contribution of electronic parameters of the ct,IB-unsaturated carbonyl fragment to the biological activity of chalcone and coumarin derivatives served as a basis for the search for ESAR in a series of synthesized benzimidazole analogs of chalcone.

Features of the reaction of heterocyclic analogs of chalcone with lanthanide shift reagents

The PMR spectra of heterocyclic analogs of 2-hydroxychalcone containing thiazole, benzofuran, triazole, imidazole, benzodioxane, or pyridine rings in the presence of lanthanide shift reagents are studied. It is found that the most effective reagent for modifying the spectra of these compounds is Yb(fod)3. The broadening of the spectra of 2-hydroxy chalcones in the presence of lanthanide shift reagents is explained by the dynamic effects of complex formation. An example is given of the determination of the conformation of molecules of 2-hydroxychalcone by the simultaneous use of lanthanide shift reagents and the homonuclear Overhauser effect.

Study of PMR spectra and structure of heterocyclic analogs of chalcone

A study was made of the PMR spectra of heterocyclic analogs of chalcone containing thiazole, imidazole, benzofuran, and pyridine residues. The shift patterns were determined of the signals under the influence of an aromatic solvent. Through experiments made on the Overhauser homonuclear effect the signals were reliably assigned and the orientation of the heterocyclic fragments in the molecules of chalcones was established.

Synthesis of derivatives of N-substitut ed pyridones from dienic monoa lkylaminoketo esters

The conversion of dienic δ-monoalkylaminoketo esters into 1-alkyl-3-acetyl-2-pyridones and 1,3-bis[3-(1-alkyl-2-pyridonyl)]-2-buten-1-ones was studied. Heterocyclic analogs of chalcone were synthesized from 1-alkyl-3-acetyl-2-pyridones.

Synthesis of new chalcone analogues and derivatives

The synthesis of new derivatives of 2′-hydroxychalcone, such as esters, sulfonates, and thiocarbamates, prepared for evaluation as antiparasitic agents as well as new heterocyclic chalcone analogues prepared for the same purpose, is described.

Comparative basicities of heterocyclic analogs of chalcone

Measurements are made of valence vibration frequency shifts of the hydroxyl group of phenol in carbon tetrachloride solution due to the effect of hydrogen bonding with the carbonyl group (ΔuOH) of chalcone, and its furan, thiophene, selenophene, and N-methylpyrrole analogs. All the compounds form rather stable hydrogen bonds with phenol; ΔuOH varies in the range 200–284 cm−1. For propen-3-ones, where the carbonyl group is remote from the heterocyclic ring, a linear relationship is observed between ΔuOH and pK α , previously determined in 100% sulfuric acid solution in glacial acetic acid. The absence of a linear relationship between these quantities for the other ketones is ascribed to steric factors. It is established that heterocyclic groups exhibit a positive conjugation effect as compared with phenol, decreasing in the order N -methyl-2-pyrryl > 2-furyl > 2-selenienyl > 2-thienyl.

Synthesis of heterocyclic analogs of chalcone containing the selenophene ring

Crotonaldehyde-type condensation using alkaline or acid catalyst is used to synthesize 14 chalcone analogs containing in addition to the selenophene ring, a number of other heterocyclic groups. A Michael adduct is shown to be formed by reaction of 2-acetylselenophene with 2-pyridine aldehyde.