A mild and atom-economical four-component cascade reaction has been developed, enabling the efficient and selective synthesis of previously inaccessible 4-hydroxyquinolin-2(1H)-one derivatives. Utilizing readily available 6-halo-4-hydroxyquinolinones, aromatic aldehydes, Meldrum’s acid, and alcohols under ʟ-proline catalysis, the reaction proceeds via in situ formation of arylidene-substituted Meldrum acids followed by sequential Michael-type addition and subsequent cascade transformations. This versatile one-pot protocol delivers structurally diverse open-chain 3-arylpropanoate esters in moderate to good yields (46–69%), while cyclic pyranoquinolinones are formed under kinetically controlled conditions. Subsequent transformations afford isopropyl and cyclohexyl analogues via hydrolysis–esterification. A preliminary biological evaluation revealed low cytotoxicity and modest antibacterial activity against Escherichia coli ΔtolC strains. This sustainable synthetic approach constitutes the first direct access to scarcely explored open-chain quinolinone esters, expanding the medicinal chemistry toolbox with promising scaffolds for drug discovery.

A novel antibacterial fluoroquinolone molecule (PFQA) that demonstrated poor solubility in the biologically relevant media was synthesized. Influence of 2-hydroxypropyl-β-cyclodextrin (HPβCD) on the physicochemical and potential biological properties of PFQA was studied. HPβCD increases the PFQA’s solubility (up to 2 times), decreases the drug’s particle size (up to 100 nm) and significantly enhances particle’s homogeneity. The mechanism of complex formation was investigated by FTIR and 1H NMR. PFQA has two binding sites for HPβCD with Kd1 = (5.8 ± 0.8) × 10–4 M and Kd2 = (2.9 ± 0.3) × 10–3 M. The negative cooperativity is possibly due to the steric effects proved in Scatchard and Hill coordinates. The results highlight the great advantage of PFQA−HPβCD comparing to free PFQA for further studies in vitro and in vivo.

BODIPY chromophores (4,4-difluoro-4-bora-3a,4a-diaza-s-indacene) are one of the most versatile fluorophores which are commonly used in a variety of scientific fields. The combination of excellent photophysical properties with the possibility of easy chemical modification of structure, chemical and photostability determines the application of BODIPY in biomedicine, photocatalysis, analytical chemistry and materials science. This review summarizes approaches to the synthesis and modification of BODIPY, discussing both classical and recently-published synthetic and postfunctionalization approaches. An influence of BODIPY structure and various postfunctionalization methods on photophysical properties of the fluorophores and their potential applications in biomedicine, materials science and biosensorics are also discussed. The bibliography includes 344 references.

The electrophilic halogenation and chalcogenation (sulfenylation and selenenylation) of endo and exo isomers of ethyl 2-azabicyclo[2.2.1]hept-5-ene-3-carboxylates bearing electron-withdrawing substituents at the nitrogen atoms with different reagents were studied. Halogenation of both endo and exo isomers gave exclusively the rearranged products. Chalcogenation of endo isomer resulted in the rearranged products, while chalcogenation of exo isomer afforded the rearranged products and 1,2-trans and 1,2-cis addition products.

Beta-lactamases are the key enzymes involved in resistance to beta-lactam antibiotics in pathogenic bacteria causing infectious diseases. The search for new inhibitors and the study of the resistance mechanisms require the production of chromogenic substrates for beta-lactamases. A novel cephalosporin derivative with an epoxy functional group named CMPD1 is synthesized. It is shown to be a substrate for TEM type beta-lactamases, which is hydrolyzed to form a colored product. The hydrolysis product has an optical absorption maximum at 450 nm. The difference in the absorption maxima of the substrate and the product is 95 nm, and, therefore, CMPD1 exceeds the previously described substrates, according to this parameter. It has been found that the CMPD1 compound is hydrolyzed only by the TEM type beta-lactamases that lack mutations in the active site. This can be used to study the mechanisms of the catalytic effect of beta-lactamases.

The novel classes of acylated phenoxyanilide and thiourea compounds were investigated for their ability to inhibit TEM type β-lactamase enzyme. Two compounds 4g and 5c reveal the inhibition potency in micromolar range and show their action by non-covalent binding in the vicinity of the TEM-171 active site. The structure activity relationship around carbon chain length and different substituents in ortho- and para-positions of acylated phenoxyanilide as well as molecular modelling study has been performed.

Reactions of electrophilic chalcogenation (sulfenylation and selenenylation) of 7-azabicyclo[2.2.1]heptadiene derivatives with electron-withdrawing substituents at the nitrogen atom and the double bond were found to proceed trans-stereospecifically with the formation of 1,2-addition products, resulting from the exo-attack by the electrophile. In the case of 2-tosyl-7-azanorbornadiene, the reaction is regiospecific: the electrophilic species exclusively adds to the carbon atom at position 6. A comparative analysis of the behavior of dimethyl bicyclo-[2.2.1]heptadiene-2,3-dicarboxylate and its 7-aza analogs in the AdE reactions was carried out.

The microbial resistance to antibiotics is a genuine global threat. Consequently, a search of new inhibitors remains of acute importance due to the increasing spread of multidrug resistance. Here we present a new type of non-β-lactam β-lactamase inhibitor PA-34 based on natural phenoxyaniline, identified using computer-assisted screening of scaffolds related to those of known low-affinity inhibitors. The compound displays reversible competitive inhibition of bacterial β-lactamase TEM-171, with a Ki of 88 μM. Using enzyme kinetics, infra-red spectroscopy, fluorescence quenching and computer docking, we propose that the inhibitor binds at the entrance to the enzyme active site. This is a novel inhibition mechanism compared to binding covalently to the catalytic serine in the active site or non-covalently to the allosteric site. The residues involved in binding the inhibitor are conserved among molecular class A β-lactamases. The identified compound and its proposed binding mode may have a potential for a regulation of the catalytic activity of a wide range of class A β-lactamases. We also hypothesise that the presented route for finding non-β-lactam compounds may be an effective and durable approach for combating bacterial antibiotic resistance.

A number of β-phenyl(or benzyl)selanyl- and β-phenylsulfanyl-substituted imines possessing an additional donor nitrogen, oxygen, or sulfur atom were synthesized by reaction of 2-phenylsulfanylethanamine, 2-phenylsulfanylcyclohexanamine, 2-phenylselanylcyclohexanamine, and 2-benzylselanylaniline with salicylaldehyde, 2-pyridinecarbaldehyde, or 2-tert-butylsulfanylbenzaldehyde. The resulting Schiff bases were tested as ligands in the complex formation with nickel(II) and copper(II), and mononuclear (L-H)MCl or LMCl2 coordination compounds were isolated (L = sulfur- or selenium-containing imine). The redox properties of the selenium-containing ligands and complexes were studied by cyclic voltammetry. The complexes were found to undergo reduction of the metal ion in two one-electron steps. The reduction is reversible for copper complexes and irreversible for nickel complexes.

A series of copper(II) and cobalt(II) complexes with novel selenium containing Schiff base ligands obtained from 2- or 3-aminoalkyl phenyl selenides and imidazole carbaldehydes have been synthesized by the interaction of corresponding organic ligands with MCl2 center dot 6H(2)O (M = Cu, Co). The crystal structure of a copper(II) complex with N-(2-(phenylseleno)ethyl)-N-(imidazolyl-2-ylmethylene)amine has been solved by a single-crystal X-ray diffraction method. The copper(II) ions are coordinated by the imine and imidazole nitrogen atoms of organic ligands and two chloride anions in a distorted square planar geometry. The electrochemical investigations of the synthesized ligands and complexes have been made by cyclic voltammetry method. It is established that the first stage of complexes reduction takes place to metal and the reduced forms of complexes are stable in the solution. (C) 2012 Elsevier Ltd. All rights reserved.

The selenoorganic ligand N-[2-(phenylseleno)cyclohexyl]-N-(pyridin-2-ylmethylene)amine and its coordination compound with CoCl2 have been obtained and investigated by cyclic voltarrunetry. The oxidation reactions of triphenylphosphine and norbornene using N2O as the oxidant and the synthesized complex as a catalyst are described.

2-Selenoimidazolidin-4-ones and 2-selenoimidazol-4-ones containing phenylor pyridylmethylidene substituent at position 5 were synthesized. The structure of 3-benzyl-2-selenohydantoine was confirmed by X-ray crystallography. A series of 2-(methylseleno)imidazol-4-ones was obtained by alkylation of 3,5-disubstituted selenohydantoines with methyl iodide. The synthesized selenohydantoines and 3-benzyl-5-pyridylmethylidene-2-(methylseleno)imidazol-4-ones were examined in the complexation reactions with CoCl2, NiCl2, CuCl2, and CuI(CH3CN)4ClO4; electrochemical investigations showed that reduced forms of the copper-containing complexes were stable