Recent developments in penta-, hexa- and heptadentate Schiff base ligands and their metal complexes

Schiff bases and their metal complexes as urease inhibitors - A brief review.

A stepwise, zwitterionic mechanism for the 1,3-dipolar cycloaddition between (Z)-C-4-methoxyphenyl-N-phenylnitrone and gem-chloronitroethene catalysed by 1-butyl-3-methylimidazolium ionic liquid cations

The zw-type [3 + 2] cycloaddition (32CA) reactions of C,N-dialkyl nitrones with a series of ethylenes of increased electrophilic character have been studied within the Molecular Electron Density Theory (MEDT) at the MPWB1K/6-311G(d,p) computational level. Both, reactivity and selectivities are rationalized depending on the polar character of the reaction. Due to the strong nucleophilic character of C,N-dialkyl nitrones, the corresponding zw-type 32CA reactions are accelerated with the increased electrophilic character of the ethylene, which also plays a crucial role in the reaction mechanism, thus determining the regio- and stereoselectivities experimentally observed. While, in the 32CA reactions with nucleophilic ethylenes, the reaction begins with the formation of the C–C single bond, determining the ortho regioselectivity, in the 32CA reactions with strong electrophilic ethylenes, the reaction begins with the formation of the C–O single bond involving the β-conjugated carbon of the ethylene, determinin...

A Molecular Electron Density Theory Study of the Reactivity and Selectivities in [3 + 2] Cycloaddition Reactions of C,N-Dialkyl Nitrones with Ethylene Derivatives.

Discovery of membrane active benzimidazole quinolones-based topoisomerase inhibitors as potential DNA-binding antimicrobial agents

An insight into synthetic Schiff bases revealing antiproliferative activities in vitro.

[2+3] Cycloaddition reactions of the highly reactive (Z)-C-(3,4,5-trimethoxyphenyl)-N-methylnitrone with (E)-2-R-nitroethenes proceed under mild conditions and yield mixtures of stereoisomeric 2-methyl-3-(3,4,5-trimethoxyphenyl)-4-nitro-5-R-isoxazolidines. The effect of regiospecificity of the cycloadditions may be accounted for by the theory of electrophilicity indexes. Stereoselectivity, however, is determined by a compilation of steric and secondary orbital effects. 
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Regio- and stereoselectivity of polar [2+3] cycloaddition reactions between (Z)-C-(3,4,5-trimethoxyphenyl)-N-methylnitrone and selected (E)-2-substituted nitroethenes

Drug resistance has become a major concern in the field of infection management, therefore searching for new antibacterial agents is getting more challenging. Our study presents an optimized and eco-friendly synthesis scheme for a panel of nitroalkenes bearing various functional groups in the aromatic moiety and bromine or cyano substituents in 1 position of nitrovinyl moiety. The presence of nitrolefine group outside the ring minimalizes genotoxic properties while conjugation of aryl group with nitrovinyl moiety increases stability of the compounds. Then our research focused on evaluation of biological properties of such obtained (E)-2-aryl-1-cyano-1-nitroethenes. As they exhibit strong bacteriostatic and bactericidal activities against reference bacteria and yeast species with no detectable cytotoxicity towards cultured human HepG2 and HaCaT cells, they could be promising candidates for the replacement of traditional nitrofurane-containing antibacterial drugs. Nevertheless, validation of the obtained data in an in vivo model and additional safety studies on mutagenicity are still required.

https://www.tandfonline.com/doi/pdf/10.3109/14756366.2015.1070264

Novel synthesis scheme and in vitro antimicrobial evaluation of a panel of (E)-2-aryl-1-cyano-1-nitroethenes.

Calcium and phosphorus are essential for skeletal mineralization and perform a wide array of other biological functions. Calcium is a prime intracellular signalling molecule. It is also involved in muscle contractions (including the myocardium), digestion and blood coagulation. (THEOBALD 2005) Phosphorus is an intrinsic constituent of many organic substances such as nucleotides, nucleosides, phosphoamino acids and proteins, phospholipids, phosphoglycans and others (HUANG, MOE 2011). In addition, it plays a critical role in cellular signalling through phosphorylation of proteins and other substances (SHAIKH et al. 2008). The present paper focuses on the role of these two elements in skeletal mineralization, and their use in treatment and medicine. First, it briefly discusses the calcium and phosphorus homeostasis, which occurs in three major organs: kidneys, intestines and bones, and involves an integrated hormonal system which maintains their normal serum levels. Moreover, disorders relevant to their abnormally high levels, hypercalcaemia and hyperphosphataemia, and excessively low levels, hypocalcaemia and hypophosphataemia, are described. Additionally, the physiology and pathology of bone as a prime store of both calcium and phosphorus are presented. Adequate intakes of these nutrients are essential for achieving the peak bone mass (PBM). A negative balance results from age-related bone loss, hence possible osteoporosis. This skeletal disorder is characterized by compromised bone strength, thus predisposing to an increased risk of fractures. One of the pharmacological interventions used in the treatment of osteoporosis is the administration of bisphosphonates. They inhibit the action of osteoclasts, prevent further bone losses and improve it strength (FERRONE, GERACI 2007). In the final part of the article, calcium phosphate basedceramics, such as coralline hydroxyapatite, calcium hydroxyapatite (HAp), tri-calcium phosphate (TCP), bioglass, calcium phosphate cements (CPC) and their clinical applications are described.

Calcium and phosphorus in medicine and treatment.

Introduction Fluorinated analogues of known biologically active compounds have been gaining increasingly more interest both from academic research institutions and large pharmaceutical companies [1÷5]. A fluorine atom or a fluorine-containing functional group incorporated into an organic compound molecule leads to major changes in physicochemical properties. It is assumed that when one hydrogen atom is substituted with a fluorine atom (or a methyl group is substituted by a trifluoromethyl group), no steric changes occur compared to the non-fluorinated molecule [6]. Therefore, considering spatial interactions the fluorinated molecule may bind the same receptors as the non-fluorinated compound. Furthermore, the high energy of the C-F bond [7, 8] prevents adverse metabolic reactions, thus increasing the stability of the compound, for example. Fluorinated analogues also exhibit increased lipophilicity and, as a result, faster diffusion through biological membranes [6, 9]. Those properties of fluorine-containing organic compounds make them important in drug synthesis. The known formulations which contain fluorinated compounds include the following anaesthetics: enflurane, isoflurane, desflurane and sevoflurane and certain anti-cancer drugs, such as 5-fluorouracil and capecitabine. The unique properties of organofluorine compounds are particularly evident when the molecule contains a xenobiotic trifluoromethyl group [10, 11]. Fluoxetine, found in the drug with a trade name of Prozac, is an example of a widely used compound containing the trifluoromethyl group. The unique properties of fluorine are seen also in ciprofloxacin, an antibacterial, in which the cell penetration rate increases 70-fold compared to its non-fluorinated analogue [12]. Fluorine substitution at a specific position in the drug molecule may affect not only pharmacokinetic properties, such as absorption, drug distribution in tissues, excretion and course and rate of biotransformation, but also its pharmacokinetics, toxicity and improved efficacy. As organofluorine compounds are rarely found in nature, organic synthesis is their primary source for pharmaceutical industry [11]. Most widely used [13] preparative approaches focus on the halogenation of aromatic moieties, while methods involving non-aromatic heterocyclic compounds are much more scarce. Halogenation reagents are usually extremely reactive which makes their safe use very difficult. Therefore, the concept of using structurally simple and commercially available starting compounds containing the CF3 group is increasingly more popular in the synthesis of more complex cyclic compounds [9]. [2+3] cycloaddition (1,3-dipolar cycloaddition) is particularly important in the methodology of organofluorine compound synthesis [14]. In the present study, data for the [2+3] cycloaddition of dipolarophiles containing CF3 groups with nitrones whose application in organic synthesis has been systematically investigated for many years [15÷19] are compared.

Agata Maziarka

Papers

An insight into synthetic Schiff bases revealing antiproliferative activities in vitro.

Regio- and stereoselectivity of polar [2+3] cycloaddition reactions between (Z)-C-(3,4,5-trimethoxyphenyl)-N-methylnitrone and selected (E)-2-substituted nitroethenes

Novel synthesis scheme and in vitro antimicrobial evaluation of a panel of (E)-2-aryl-1-cyano-1-nitroethenes.

Calcium and phosphorus in medicine and treatment.

Trifluormethylalkenes in [2+3] cycloaddition reactions with nitrones