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A series of 20 newly designed (E)-1-(4-sulphamoylphenylethyl)-3-arylidene-5-aryl-1H-pyrrol-2(3H)-ones was synthesised and assessed as carbonic anhydrase (CA, EC 4.2.1.1) inhibitors towards four human isoforms of pharmaceutical interest, that is, hCA I, II, IX and XII. The compounds displayed low to high nanomolar potency against all the isoforms. Introducing strong electron withdrawing groups at the para position of the arylidene ring increased the binding affinity to the enzyme. All compounds showed acceptable pharmacokinetic range and physicochemical characteristics as determined by computational ADMET analysis. Density Functional Theory (DFT) calculations of 3n were carried to gain understanding on the stability of the E and Z isomers. The energy values clearly indicate the stability of E isomer over Z isomer by −8.2 kJ mol−1. Our findings indicate that these molecules are useful as leads for discovering new CA inhibitors. [ABSTRACT FROM AUTHOR]

Some pyrazole-based heterocycles such as pyrrolone, pyridazinone, and imidazole derivatives were synthesized utilizing the pyrazolyl-2(3H)-furanone derivative 3, which was obtained in a good yield via Perkin condensation of 5-chloro-4-formyl-3-methyl-1-phenylpyrazole with 3-(4-methylbenzoyl)propionic acid in the presence of cyclo-dehydrating agent (sodium acetate and acetic anhydride). Also, the acid hydrazide obtained was reacted with some carbonyl reagents such as acetic anhydride, benzoyl chloride, 4-chlorobenzaldehyde, and 1,3-diphenyl-4-formylpyrazole, aiming to achieve new pyrrolone derivatives. The antioxidant, antimicrobial, and antiviral activity screening of some synthesized compounds demonstrated that some of them offered strong potencies. An experimental trial was undertaken to explore the effect of different substances and applied against avian influenza HPAI-H5N1 (AIV) to evaluate the antiviral replication in specific pathogen-free chicken embryos. All the compounds were screened for their antimicrobial activities, and most of tested compounds showed potent inhibition growth activity toward Haemophilus (Gram-negative bacteria), Staphylococcus aureus (Gram-positive bacteria), and Candida albicans fungus. Upon antimicrobial screening, it was observed that the majority of the compounds were found to be active against Staphylococcus aureus, Haemophilus, and Candida albicans as compared to standard drugs. This experiment shows the potential usage of these compounds as antiviral agents and can be considered as a viable means to control the economically important avian influenza of poultry. These compounds can thus be recommended for their antiviral, antibacterial, and antifungal property and can very well be used as immunostimulants. [ABSTRACT FROM AUTHOR]

Nitrogen heterocycles are a class of organic compounds with extremely versatile functionality. Imidines, HN[C(NH)R]2, are a rare class of heterocycles related to imides, HN[C(O)R]2, in which the O atoms of the carbonyl groups are replaced by N—H groups. The useful synthesis of the imidine compounds succinimidine and glutarimidine, as well as their partially hydrolyzed imino–imide congeners, was first described in the mid‐1950s, though structural characterization is presented for the first time in this article. In the solid state, these structures are different from the proposed imidine form: succinimidine crystallizes as an imino–amine, 2‐imino‐3,4‐dihydro‐2H‐pyrrol‐5‐amine, C4H7N2 (1), glutarimidine as 6‐imino‐3,4,5,6‐tetrahydropyridin‐2‐amine methanol monosolvate, C5H9N3·CH3OH (2), and the corresponding hydrolyzed imino–imide compounds as amino–amides 5‐amino‐3,4‐dihydro‐2H‐pyrrol‐2‐one, C4H6N2O (3), and 6‐amino‐4,5‐dihydropyridin‐2(3H)‐one, C5H8N2O (4). Imidine 1 was also determined as the hydrochloride salt solvate 5‐amino‐3,4‐dihydro‐2H‐pyrrol‐2‐iminium chloride–2‐imino‐3,4‐dihydro‐2H‐pyrrol‐5‐amine–water (1/1/1), C4H8N3+·Cl−·C4H7N3·H2O (1·HCl). As such, 1 and 2 show alternating short and long C—N bonds across the molecule, revealing distinct imino (C=NH) and amine (C—NH2) groups throughout the C—N backbone. These structures provide definitive evidence for the predominant imino–amine tautomer in the solid state, which serves to enrich the previously proposed imidine‐focused structures that have appeared in organic chemistry textbooks since the discovery of this class of compounds in 1883. [ABSTRACT FROM AUTHOR]

Some pyrazole-based heterocycles, such as pyrrolone, pyridazinone, and imidazole derivatives were synthesized utilizing the pyrazolyl-2(3H)-furanone derivative 3, which was obtained in a good yield via Perkin condensation of 5-chloro-4-formyl-3-methyl-1-phenylpyrazole with 3-(4-methylbenzoyl)propionic acid in the presence of cyclo-dehydrating agent (sodium acetate and acetic anhydride). Also, the acid hydrazide obtained was reacted with some carbonyl reagents like acetic anhydride, benzoyl chloride, 4-chlorobenzaldehyde, and 1,3-diphenyl-4-formylpyrazole, aiming to achieve new pyrrolone derivatives. The antioxidant activity screening of some synthesized compounds demonstrated that pyridazinone and N-phenylhydrazide derivatives showed the most exceptional potencies. [ABSTRACT FROM AUTHOR]

The title compound, [Fe(C5H5)(C21H24NO2)], which is produced by the oxidation of 1-(4-tert-butylphenyl)-2-ethyl-3-ferrocenylpyrrole, crystallizes as a racemic mixture in the centrosymmetric space group P21/n. The central heterocyclic pyrrole ring system subtends dihedral angles of 13.7 (2)° with respect to the attached cyclopentadienyl ring and of 43.6 (7)° with the major component of the disordered phenyl group bound to the N atom. The 4-tertbutylphenyl group, as well as the non-substituted Cp ring are disordered with s.o.f. values of 0.589 (16) and 0.411 (16), respectively. In the crystal, molecules with the same absolute configuration are linked into infinite chains along the baxis direction by O--H· · ·O hydrogen bonds between the hydroxy substituent and the carbonyl O atom of the adjacent molecule. [ABSTRACT FROM AUTHOR]

A series of benzimidazole-tethered pyrrolones and N-benzylpyrrolones were synthesized, charac-terized, and explored for their in vitro anti-proliferative activities. The cytotoxicity of the synthesized com-pounds was evaluated against three cancer cell lines, A549, MCF7, and DU145. (E)-5-(1H-Benzimidazol-2-yl)-3-(3,4,5-trimethoxbenzylidene)-1H-pyrrol-2(3H)-one having three methoxy groups at 3,4,5-positions exhibited excellent activity against A549, MCF7, and DU145 cancer cell lines with IC50 values of 8.3±0.53, 7.2±1.42, and 7.7±0.13 µM, respectively. Another pyrrolone derivative with one hydroxy and one methoxy substituents, (E)-5-(1H-benzimidazol-2-yl)-3-(4-hydroxy-3-methoxybenzylidene)-1H-pyrrol-2(3H)-one, also displayed very good activity against A549, MCF7, and DU145 cell lines with IC50 values of 9.6±0.12, 7.3±0.24, and 8.7± 0.24 µM, respectively. Molecular docking study revealed that all compounds fit into the pocket of VEGFR-2 within the key amino acid residues Glu885, Cys919, and Asp1046. The docking scores and binding energies were very consistent with the experimental anticancer activity. Pharmacokinetic (ADME) parameters of the potent derivatives were also found to be within an acceptable range. It could be concluded that benzimidazole-linked pyrrolones are more potent than their benzylpyrrolone analogs, and therefore this class of compounds could be explored further for the development of potent anticancer agents. [ABSTRACT FROM AUTHOR]

Arylidene‐Δ2‐pyrrolin‐4‐ones undergo organocatalyzed annulation with malononitrile, furnishing dihydropyrano[3,2‐b]pyrroles (18 examples, 0–77% ee in dichloromethane, 11–44% ee in methanol). The products could be enantiomerically enriched by trituration (11 examples, 95–99% ee). Enantioselectivity was dependent on the nature of the substrate and the conformation of the catalyst, which in turn was solvent‐controlled. The reaction mechanism, which included two pseudo‐enantiomeric organocatalyst conformations, was investigated by experimental and quantum chemical methods. The reaction mechanism consists of Michael addition reaction step followed by 6‐exo‐dig annulation, which was found to be the rate determining step. Additionally, it was identified that the preferred reaction pathway follows the model originally proposed by Pápai et al. [ABSTRACT FROM AUTHOR]

The furanone 1 was allowed to react with different nitrogen nucleophiles such as hydrazine hydrate, hydroxyl amine, anisidine, anthranilic acid, glycine, ethylglycinate and isatin and some carbon nicleophiles under Michael reaction conditions assisted by microwave irradiation. They afforded new synthesized some important heterocyclic compounds 2–16. The structures of the synthesized new compounds were characterized by spectral data and elemental analysis. DFT calculation is serving to clarify not only the active electrophilic sites attacked by suitable nucleophiles in the organic reaction but also the bioactivity of the larvicidal compounds. The larvicidal activities of the synthesized compounds were tested against Plutella xylostella and Helicoverpa armigera larvae in vitro. The results revealed that the synthesized compounds 4, 13 and 14 showed good insecticidal activity against Plutella xylostella larvae with 100%, 87.2% and 91.4% activities, respectively, while 13 and 14 displayed 92% and %, 94.8 activities, respectively, against Helicoverpa armigera larvae. Therefore, they exhibited good larvicidal activity. The executed molecular docking simulations evinced the selective binding of the novel synthesized compounds toward acetylcholinesterase (AchE) of Drosophila Melanogaster, which signifies their role as a prominent larvicides. Compound 4, 13 and 14 showed clear docking affinity and to the assumed binding sites in terms of both calculated binding energies and the types of interactions, which provided a solid rationalization for the conducted experimental results. [ABSTRACT FROM AUTHOR]

In the 20th century, many new drugs have been designed and synthesized to be used for therapeutic purposes. In these syntheses, especially the salicylic acid group is included in the structure of many drugs. The salicylic acid molecule is the starting material of aspirin and is a structurally important compound. There are many commercial products on the market that are synthesized from salicylic acid or contain salicylic acid group. In this study, the synthesis of salicylic acid- pyrrolone hybrid compounds was carried out from the reactions of furan-3-one compounds with 4-aminosalicylic acid and 5-aminosalicylic acid reagents. The synthesis reactions were achieved in three steps and in these synthesis, biologically active pyrrolone and salicylic acid groups were integrated. The characterizations of these compounds that were purified by column chromatography and crystallization method were made by FTIR, NMR and HRMS techniques. The cytotoxic and genotoxic potentials of the novel compounds (7a-e) were evaluated at five different concentrations (6.25, 12.5, 25, 50 and 100 μM) using the Allium test system. As a result of cytogenetic analysis, it was determined that high concentrations of some hybrid compounds significantly reduced the number of divisions of A. cepa cells (cytotoxicity in 7a and 7c) and caused chromosomal abnormalities in dividing cells (genotoxicity in 7a, 7c, 7e, and especially 7d). [ABSTRACT FROM AUTHOR]

A key step during the biosynthesis of cytochalasans is a proposed Knoevenagel condensation to form the pyrrolone core, enabling the subsequent 4+2 cycloaddition reaction that results in the characteristic octahydroisoindolone motif of all cytochalasans. In this work, we investigate the role of the highly conserved α,β‐hydrolase enzymes PyiE and ORFZ during the biosynthesis of pyrichalasin H and the ACE1 metabolite, respectively, using gene knockout and complementation techniques. Using synthetic aldehyde models we demonstrate that the Knoevenagel condensation proceeds spontaneously but results in the 1,3‐dihydro‐2H‐pyrrol‐2‐one tautomer, rather than the required 1,5‐dihydro‐2H‐pyrrol‐2‐one tautomer. Taken together our results suggest that the α,β‐hydrolase enzymes are essential for first ring cyclisation, but the precise nature of the intermediates remains to be determined. [ABSTRACT FROM AUTHOR]

The broad spectrum of biological activity of quinoline derivatives coupled with our interest in the chemistry of furanones led us to synthesize a quinoline derivative bearing a 2(3H)-furanone scaffold. This derivative was used as a key starting material for the construction of some pyrrolone, imidazole, and pyridazinone derivatives obtained by reactions with some nitrogen nucleophiles viz. ammonium acetate, benzylamine, 1,2-diaminoethane, and hydrazine hydrate. The hydrazide obtained was condensed with 3-chlorobenzaldehyde, 1,3-diphenyl-1H-pyrazole-4-carbaldehyde, isatin, and dodecanoyl chloride to achieve the corresponding hydrazone and pyrrolone derivatives. Also, the synthesized compounds were evaluated for their in vitro antitumor activity using two cancer cell lines: breast and colon tumors. Some compounds displayed satisfactory activities. [ABSTRACT FROM AUTHOR]

In the present work, 3-benzylidenefuran 2 and 3-benzylideneisobenzofuran 3 derivatives were investigated in a comparative study in which they were utilized as building blocks to construct different heterocyclic compounds. Therefore, they were allowed to react with different nitrogen and oxygen nucleophiles under the same conditions to afford some novel compounds 4-16. All the structures of the synthesized compounds 2-16 were elucidated based on their elemental analyses and spectral measurements. The bioactivities of the synthesized compounds were evaluated, where some of tested compounds exhibited promising antimicrobial, antitumor, and antioxidant activities. [ABSTRACT FROM AUTHOR]

A 2(3H)-furanone bearing chromonyl moiety at position-3 was synthesized and utilized for the construction ofN-heterocycles such as pyrrolone,N-aminoquinolone, and pyridazinone derivatives. The reactivity of the chromonylfuranone toward some nitrogen nucleophiles such as ammonia, benzylamine, hydrazine, and phenylhydrazine was studied. On the other hand, thiation of the starting chromonylfuranone interestingly provides mono- and di-thiated products. The chemoselectivity of these reactions is discussed. The structures of all products obtained were elucidated from their analytical and spectral data. The antimicrobial activities of selected examples of the synthesized compounds were examined against two strains of bacteria and two fungus strains. Some of them showed promising antimicrobial activities. [ABSTRACT FROM AUTHOR]

A new protocol for the one-pot synthesis of pyrrolones and butenolides involving an isocyanide-based multicomponent reaction (Ugi or Passerini) followed by a triethylamine-promoted cycloisomerization is described. [ABSTRACT FROM AUTHOR]

A series of new pyrrol-2(3 H )-ones 4a-f and pyridazin-3(2 H )-ones 7a-f were synthesized and characterized using different spectroscopic tools. Some of the tested compounds revealed moderate activity against 60 cell lines. The E form of the pyrrolones 4 showed good cytotoxic activity than both the Z form and the corresponding open amide form. Furthermore, the in vitro cytotoxic activity against HepG2 and MCF-7 cell lines revealed that compounds ( E )4b , 6f and 7f showed good cytotoxic activity against HepG2 with IC 50 values of 11.47, 7.11 and 14.80 μM, respectively. Compounds ( E )4b , 6f , 7d and 7f showed a pronounced inhibitory effect against cellular localization of tubulin. Flow cytometric analysis indicated that HepG2 cells treated with ( E )4b showed a predominated growth arrest at the S-phase compared to that of G2/M-phase. Molecular modeling study using MOE® program indicated that most of the target compounds showed good binding of β-subunit of tubulin with the binding free energy (dG) values about −10 kcal/mole. [ABSTRACT FROM AUTHOR]

2-(2-Bromovinyl)benzimidazoles are carbonylatively cyclized under carbon monoxide pressure in toluene in the presence of a catalytic amount of PdCl 2 and PPh 3 along with a base to give 1 H -benzo[ d ]pyrrolo[1,2- a ]imidazolones in good yields. [ABSTRACT FROM AUTHOR]

Abstract: A CuCl2-catalyzed dehydrogenative C–H activation leading to regioselective synthesis of coumarin, quinolone, and naphthalene fused heterocycles is reported. The reaction has been carried out in one pot under open atmosphere and it offers good to excellent yields of the cyclized products. [Copyright &y& Elsevier]

The article discusses a study which examines the formation of dilysyl-dipyrrolones (dilysyl-DPLs) from xylose and amino acids with lysine. Findings reveal that the development was achieved during weak acidic conditions. It also highlights several DPL derivatives which were determined in the study including alanine, glutamic acid, and leucine.

In the present investigation, 17 new synthetic butenolides, i.e. 2-arylidene-4-(4-chloro/ethyl-phenyl)but-3-en-4-olides ( 3–19) have been synthesized from 3-(4-chloro-benzoyl)propionic acid or 3-(4-ethyl-benzoyl)propionic acid using appropriate reagents. Some of the selected butenolides were reacted with ammonia and benzylamine to give the corresponding pyrrolones ( 20–31) and N-benzyl-pyrrolones ( 32–39) respectively. All the compounds were screened for their antibacterial activity against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa and antifungal activity against Candida albicans, Aspergillus niger, and Rhizopus oryza. Minimum inhibitory concentration (MIC) values of the compounds are reported. The pyrrolone derivatives discovered in this study may provide valuable therapeutic intervention for the treatment of microbial diseases, especially against fungal species. [ABSTRACT FROM AUTHOR]

The article presents a study on the isolation of two novel yellow compounds from a solution with xylose and lysine. It notes how compounds with xylose and L-lysine reacted to Maillard reaction in which these compounds turn brown. Various methods are used to identify the compounds named dilysyldipyrrolones A and B such as instrumental analyses, browning of amino acids, and estimation of color intensity. Results identified the major yellow pigments in the heated solution of xylose and lysine.

3-Arylidene-5-(4-methylphenyl)-2(3H)-furanones 2a-m were prepared from 3-(4-methyl-benzoyl)propanoic acid 1 and several aromatic aldehydes. Some of the selected furanones were reacted with ammonia gas and benzylamine to give corresponding 3-arylidene-1,3-dihydro-5-(4-methylphenyl)-2H-pyrrol-2-ones 3a-h and 3-arylidene-1-benzyl-1,3-dihydro-5-(4-methylphenyl)-2H--pyrrol-2-ones 4a-f, respectively, which were characterized on the basis of IR, ¹H-NMR, mass spectral data and elemental analysis results. These compounds were tested for their anti-inflammatory and antibacterial activities. The compounds, which showed significant anti-inflammatory activity, were further screened for their analgesic and ulcerogenic activities. Three new compounds (2e, 2h and 4d), out of twenty-seven showed very good anti-inflammatory activity in the carrageenan induced rat paw edema test, with significant analgesic activity in the acetic acid induced writhing test together with negligible ulcerogenic action. The antibacterial activity is expressed as the corresponding MIC values. [ABSTRACT FROM AUTHOR]

Abstract: 2-Arylidene-4-(4-phenoxy-phenyl)but-3-en-4-olides (1–17) were prepared from 3-(4-phenoxy-benzoyl)propionic acid and aromatic aldehydes. Some of the selected butenolides were reacted with ammonia and benzylamine to give corresponding 3-arylidene-5-(4-phenoxy-phenyl)-2(3H)-pyrrolones (18–23) and 3-arylidene-5-(4-phenoxy-phenyl)-1-benzyl-2(3H)-pyrrolones (24–29) respectively, which were characterized on the basis of 1H-, 13C-NMR, Mass spectrometric data and elemental analysis results. These compounds were tested for anti-inflammatory and antimicrobial actions. The compounds, which showed significant anti-inflammatory activity, were screened for their analgesic and ulcerogenic activities. Five new compounds (5, 6, 7, 25 and 26), out of 29 showed very good anti-inflammatory activity in the carrageenan induced rat paw edema test, with significant analgesic activity in the acetic acid induced writhing test together with negligible ulcerogenic action. Antibacterial activity against Staphylococcus aureus and Escherichia coli as well as antifungal activity against Candida albicans were expressed as the corresponding minimum inhibitory concentration (MIC) values. Compound 21, 22 and 23 showed excellent activity against C. albicans with MIC-10 μg/ml. Out of the above-mentioned compounds, 22 and 23 also showed good activity against S. aureus with MIC-20 and 15 μg/ml respectively. [Copyright &y& Elsevier]

Ten undescribed alkaloids, named integerrines A–J, including one racemic heterodimer of carbazole and indole, two racemic, two scalemic, and one enantiomerically enriched biscarbazoles, two aldoximes, and one racemic pyrrolone, were isolated from the dried leaves and stems of Micromelum integerrimum. The racemic or scalemic compounds were resolved using chiral-phase HPLC and their configurations were determined by comparison of experimental and calculated ECD data. Four compounds exhibited moderate to weak cytotoxicities against HepG2, HTC-116, HeLa, and PANC-1 cell lines, with IC 50 values of 14.1–67.5 μM. Ten undescribed alkaloids named integerrines A–J were isolated from Micromelum integerrimum (Buch.-Ham.) Roem. Image 1 • Ten undescribed alkaloids were isolated from Micromelum integerrimum. • A racemic heterodimer of carbazole and indole was firstly obtained. • Two rare natural aldoximes were isolated. • A racemic pyrrolone was isolated. • Four compounds showed cytotoxicities against four tumor cell lines. [ABSTRACT FROM AUTHOR]