Waldemar Tejchman

SELENOMALTOL -SYNTHESIS, SPECTROSCOPY AND THEORETICAL CALCULATIONS

- Synthesis and structure of the seleno derivative of maltol (selenomaltol) is described. Structural and energetical properties of possible selenomaltol structures have been calculated at the B1LYP/6-311++G(d,p) level. The lowest energies are always predicted for the keto-enol tautomer. To verify obtained results several standard experimental methods, namely: elemental analysis, mass spectrometry, infrared and NMR spectroscopies and X-ray crystallography have been used. Investigation of IR and NMR spectra clearly indicate that the oxygen atom of exocyclic keto group on maltol was replaced by selenium. Experimental crystallographic results support this conclusion.

The Synthesis and Crystal Structures of the Homologues of Epalrestat

Two homologues of epalrestat were synthesized and characterized by IR, MS, elemental analysis, 1H NMR, 13C NMR and their crystal structures were determined by X-ray diffraction method. The crystals of both compounds belong to the triclinic centrosymmetric space group. In both crystal structures the carboxyl groups are involved in the strong O–H···O hydrogen bonds. One compound crystallizes together with the dimethylformamide molecules from the solvent, forming with them intermolecular hydrogen bonds. In this crystal structure the disorder of solvent molecule is observed. The packing of the second compound is determined by hydrogen bonds between carboxyl groups leading to formation of characteristic molecular pairs. In addition, the crystal structures are also stabilized by weak contacts C–H···O and C–H···S. Both crystal structures were compared to that of the epalrestat determined earlier. The investigated compounds differ in planarity of molecules in comparison to epalrestat, but the same isomer and the extended conformation as in epalrestat molecule, are observed.Graphical AbstractTo study the conformations and intermolecular interactions of potential inhibitors of aldose reductase two homologues of epalrestat were synthesized and their crystal structures were determined by single crystal X-ray diffraction method. The first homologue forms strong hydrogen bonds via carboxyl group with DMF from the solvent, whereas the second builds homosynthons by intermolecular interaction of two molecules via carboxyl groups.

Synthesis of 1,4,6-Trisubstituted 2[1H]-Pyrimidineselenones

1,6-Diaryl-4-methyl-2[1H]-pyrimidineselenones and 1,4-diaryl-6-methyl-2[1H]-pyrimidineselenones were synthesised by treatment of appropriate pyrimidinethiones with gaseous H 2 Se. 2D NMR spectroscopic studies were conducted to obtain conformations of the newly synthesised derivatives.

Antibacterial properties of 5-substituted derivatives of rhodanine-3-carboxyalkyl acids

A series of rhodanine 3-carboxyalkanoic acid derivatives possessing 4′-(N,N-dialkyl-amino or diphenylamino)-benzylidene moiety as a substituent at the C-5 position were synthesised and their antibacterial activity was screened. All the rhodanine derivatives showed bacteriostatic or bactericidal activity to the reference gram-positive bacterial strains, but lack of activity to the reference Gram-negative bacterial strains and yeast strains was observed.

The Crystal Structures of Three Rhodanine-3-Carboxylic Acids

The rhodanine derivatives show various pharmacological activities. Rhodanine-3-carboxylic acids can be used as the substrates in various synthesis of compounds containing rhodanine-3-carboxyalkyl moiety. In this paper new crystal structures of rhodanine-3-acetic acid and its two homologues, i.e. rhodanine-3-propionic acid and rhodanine-3-butyric acid, are reported. The relationship between the length of the alkyl chain and the geometry of these molecules was studied. The crystal network is dominated by strong hydrogen bonds O–H···O formed by the carboxyl groups. Additionally, weak C–H···O and C–H···S contacts are observed.Graphical AbstractTo study the difference in intermolecular interactions of rhodanine-3-carboxylic acid, three crystal structures were determined by X-ray diffraction method. The crystal network in all studied structures is built of homosynthons and stabilized by weak C–H···O and C–H···S contacts.

Chromatographic and Computational Studies of Molecular Lipophilicity and Drug-likeness for few 2-Thioxo-1,3-Thiazolidin-4-one Derivatives and their Analogs

Hydrophobicity of the eight 2-thioxo-1,3-thiazolidin-4-one derivatives was determined experimentally by thin-layer chromatography and predicted by means of commercially available programmers. RM values were determined by reversed-phase thin-layer chromatography with using acetonitrile-water, methanol-water, acetone-water, propan-2-ol-water or 1,4-dioxane-water and compared with logP values calculated by using computer programs: HyperChem 8.0.10, Virtual Chemical Calculation Laboratory, ACD/LogP. The drug-likeness has been calculated using Molinspiration. All the heterocycles were found to obey Lipinskis rule of 5 for an orally active drug.

Exocyclic Sulfur and Selenoorganic Compounds Towards Their Anticancer Effects: Crystallographic and Biological Studies

Background/Aim: Multidrug resistance leads to therapeutic difficulties. There is great interest in experimental chemotherapy regarding multidrug resistance inhibitors and new anticancer agents. The aim of this study was to evaluate the anticancer activity of exocyclic sulfur and selenoorganic compounds on mouse T-lymphoma cell lines. Materials and Methods: A series of eighteen sulfur and selenium analogues of 2[1H]-pyrimidinone and hydantoin derivatives were evaluated towards their efflux modulating, cytotoxic and antiproliferative effects in mouse T-lymphoma cells. The combination assay with doxorubicin on multidrug resistant mouse T-lymphoma cells was performed in order to see the nature of drug interactions. Crystal structures were determined for two selected compounds with the highest efflux-modulating activity. Results: The sulfur analogues with aromatic rings almost perpendicular to pyrimidinethione ring at positions 1 and 6 showed the highest efflux inhibitory action, while all selenium analogues showed good antiproliferative and cytotoxic activities. Conclusion: The sulfur analogues can be modified towards improving their efflux inhibitory activity, whereas the selenium towards antiproliferative and cytotoxic activities.