Agneš Kapor

Synthesis and biological evaluation of new pyrazole- and tetrazole-related C-nucleosides with modified sugar moieties

Abstract 3(5)-Carboxamido-4-(β- d -ribofuranosyl)pyrazoles bearing 2′-benzamido ( 15 ) and 3′-mesyloxy ( 29 ) isosteric groups, as well as the tetrazole C -nucleosides with 2-benzamido-2-deoxy-β- d -ribofuranose ( 19 ) and 3-azido-3-deoxy-β- d -xylofuranose ( 36 ) as sugar segments, have been synthesized starting from d -glucose, by utilizing the 2,5-anhydro- d -glucose ethylene acetal derivatives 1 and 20 as divergent intermediates. The C -nucleosides 15 and 36 were shown to be moderate inhibitors of the in vitro growth of both N2a and BHK 21 tumour cell lines, whereas 29 showed a selective, although not potent cytotoxic activity against N2a cells. Compound 29 also showed a moderate in vitro antiviral activity towards the rabies virus.

Inclusion complexes of amlodipine besylate and cyclodextrins

AbstractIn this paper the procedure for the preparation of inclusion complexes of amlodipine besylate with β-cyclodextrin (β-CD) and 2-hydrohypropyl-β-cyclodextrin (HPβ-CD) and their structural characterization was described. Molecular inclusion complexes of amlodipine besylate are prepared by the coprecipitation method and characterised by the application of spectroscopic methods FTIR, 1H-NMR and XRD. The photosensitivity of amlodipine besylate in the inclusion complexes was also determined with respect to uncomplexed agent. DSC curves indicate the loss of the clear peak due to melting of amlodipine besylate at about 200°C, while on XR diffractograms certain reflections are lost belonging to amlodipine besylate in complexes. This indicates its inclusion in the vacancies of the host. The inclusion of amlodipine besylate with cyclodextrins increases the stability, i.e. decreases the photosensitivity of amlodipine besylate.

Classification of stacking interaction geometries of terpyridyl square-planar complexes in crystal structures

Stacking interactions of terpyridyl square-planar complexes in crystal structures were studied analyzing data from the Cambridge Structural Database. In most of the crystal structures, two terpyridyl complexes were oriented “head-to-tail” or “head-to-head”, with “head-to-tail orientation” being most prevalent. The number of structures with other orientations was very small. Based on the analysis of interacting geometries, we classified overlaps of terpyridyl complexes into six types. The types were defined by values of several geometrical parameters and all interactions of the same type had very similar overlap patterns.

Inclusion complexes of sulfanilamide with β-cyclodextrin and 2-hydroxypropyl-β-cyclodextrin

Sulfanilamide belongs to the group of drugs that have a bacteriostatic effect on different pathogenic microorganisms. This activity originates from the competitive antagonism with p-aminobenzoic acid, which is an integral part of folic acid. The safe use of sulfanilamide is limited due to poor solubility in the aqueous medium. Therefore, the aim of this paper is the synthesis of sulfanilamide, as well as preparing and structural characterization of its inclusion complexes with cyclodextrins. The crude sulfanilamide was obtained in the synthesis between acetanilide and chlorosulfonic acid according to the standard procedure. The synthesized sulfanilamide was recrystallized from water in order to obtain the satisfactory purity of the substance. Sufanilamide was complexed with β-cyclodextrin and 2-hydroxypropyl-β-cyclodextrin by the co-precipitation method. A molecular encapsulation of sulfanilamide was confirmed by using FTIR, 1H-NMR, XRD and DSC methods. Phase-solubility techniques were used to assess the formation of the inclusion complex between sulfanilamide and cyclodextrins. The photostability of sulfanilamide and its inclusion complexes was estimated by UVB irradiation in a photochemical reactor by applying the UV–Vis method. Based on the UV–Vis analysis, sulfanilamide:2-hydroxypropyl-β-cyclodextrin complex was presented as more photostable than sulfanilamide:β-cyclodextrin complex and sulfanilamide. The obtained results enable the potential use of these inclusion complexes for the preparation of oral formulations due to the enhanced solubility of sulfanilamide.

The protection of Nifedipin from photodegradation due to complex formation with β-cyclodextrin

AbstractThe inclusion complex β-cyclodextrin:nifedipin was prepared in solid state by coprecipitation with 1:1 mol ratio. The structure of the obtained complex and nifedipin was characterized by use of X-ray diffraction (XR), infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR), and differential scanning calorimetry (DSC) methods. The photodegradation of nifedipin and the β-cyclodextrin:nifedipin inclusion complex in solid state was monitored under natural daylight by infrared spectroscopy, whereby the free nifedipin degraded four to five times faster than the complexed nifedipin. The photodegradation products of both free and complexed nifedipin, formed during irradiation at 350 nm (with corresponding energy flux of 18 W m−2) were monitored by liquid chromatography during various time intervals. The speed of formation of nitroso- and nitro-phenyl derivatives by nifedipin irradiation was significantly higher than those of complexed nifedipin irradiation, which indicates its increased photostability in the inclusion complex. The effect on this property is significant because it contributes both to the improvement of the therapeutic effect of nifedipin and to the safer application thereof.

The canal inclusion complex of allicin with carbamide: Preparation, characterization and microbiological investigation

The carbamide:allicin canal inclusion complex was prepared in the solid state. The structure of the complex obtained was characterized by x-ray crystallography, infrared spectroscopy and thermogravimetric analysis. The microbiological activities of the inclusion complex and allicin were investigated and compared with respect to fungi (Candida albicans ATCC 10231 and Aspergillus niger ATCC 16404) and bacteria (Staphylococcus aureus ATCC 6538, Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 9027). It was found that the inclusion complex inhibited the growth of bacteria and fungi for a longer period than allicin in the free state.

The influence of water molecule coordination onto the water–aromatic interaction. Strong interactions of water coordinating to a metal ion

The interactions between water molecules (non-coordinating and coordinating) and aromatic rings were studied by analyzing data in the Cambridge Structural Database and by quantum chemical calculations. The results show the influence of water coordination to a metal ion; interactions of coordinating water are stronger. The MP2/def2-QZVP interaction energies of non-coordinating water and neutral aqua complexes [ScCl3(H2O)3], [ZnCl2(H2O)4], [CdCl2(H2O)4], and [ZnCl2(H2O)2] with benzene molecule are −3.36, −5.10, −5.43, −6.86, and −5.14 kcal mol−1, respectively. Interactions of charged aqua complexes [ZnCl(H2O)5]+ and [Zn(H2O)6]2+ are stronger, −9.69 and −13.96 kcal mol−1, respectively. The calculations also reveal strong long-range interactions: at the distance of 3.0 A the interaction energies of neutral complexes are in the range of −4.11 to −4.91 kcal mol−1, while interaction energies of charged complexes are −6.37 and −10.76 kcal mol−1.

X-Ray Crystal Structure of 10β-Hydroxy-4β,5β-epoxyestr-1-en-3,17-dione and Antitumor Activity of its Congeners

Based on the biological properties of epoxyquinols from natural sources, the title compound was synthesised as a potential antitumor agent. Its molecular structure was partially confirmed by NMR studies. The detailed structure was established by X-ray analysis revealing two symmetry independent molecules in the asymmetric unit each consisting of four fused rings with the C(10) β-oriented hydroxy group and β-oriented O atom bridging C(4) and C(5). The conformation of A ring in both conformers A and B is boat (B3,6), while rings B and C are chairs (1C4) and the five-membered D ring is in an envelope (E2) conformation. The in vitro antitumor activity of title compound and its 17b-acetoxy analogue against HeLa and Fem-x cells revealed IC50 values of 5.7 and 7.1 mM, and 2.25 and 1.58 mM, respectively. Corresponding quinols were tested on 47 cell lines with 10b-hydroxy-17β-acetoxyestra-1,4-dien-3-one being most active against leukemia SR cells (GI50 = 0.17 mM).

Antioxidant capacity of Melampyrum barbatum – weed and medicinal plant

This study was designed to examine antioxidant and free radical scavenging activities of red and yellow forms of Melampyrum barbatum L. In this study, we report the results concerning flower and leaf antioxidant enzyme activities (superoxide dismutase, catalase, guaiacol peroxidase and glutathione peroxidase), reduced glutathione quantity, flavonoids, photosynthetic pigments and soluble protein contents and quantities of malonyldialdehyde, •OH and O2•− radicals; total antioxidant capacity was determined by FRAP (Ferric Reducing Antioxidant Power) method and scavenger activity by DPPH (1,1‐diphenyl‐2‐pycril‐hydrasil radical) method. Lipofuscin ‘plant age pigments’ were also determined. According to our results, flowers of the red form of M. barbatum exhibited the highest antioxidant capacity. Copyright

The improved photostability of naproxen in the inclusion complex with 2-hydroxypropyl-β-cyclodextrin

The aim of this work was the preparation of the inclusion complex of naproxen with 2hydroxypropyl-β-cyclodextrin (HP-β-CD) in order to improve the physical and chemical properties of naproxen. The molecular inclusion complexes of naproxen with HP-β-CD were prepared by using the co-precipitation method in the solid state with the molar ratio of 1:1. The structure of the obtained complex was characterized by using FTIR, 1 H NMR, UV-Vis and XRD methods. The testing of naproxen photostability by the UV-Vis method indicated the degradation to aromatic ketone, 2-acetyl-6-methoxynaphthalene. FTIR analysis showed that the degradation has started 15 days after the exposure of naproxen to daylight while the inclusion complex of naproxen:2-hydroxypropyl-β-cyclodextrin was photostable for a period of 30 days.