Piperazine nucleus is one of the most important heterocyclic systems exhibiting remarkable pharmacological activities. Thus, in the current study six new aryl/aralkyl substituted piperazine derivatives, containing methylxanthine moiety were synthesized and their structures were confirmed by IR and 1H NMR analysis. All compounds were in vitro screened for their activity as antioxidants using DPPH (2,2′-Diphenyl-1-picrylhydrazyl), ABTS (2,2′-azinobis-(3-ethylbenzo thiazine-6-sulfonic acid)) and FRAP (ferric reducing/antioxidant power) methods. The antioxidant activity of the studied compounds against lipid peroxidation was also measured. The highest antioxidant activity was demonstrated by compound 3c. It is obvious that the presence of a hydroxyl group in the structure is essential for the antioxidant properties and should be taken into consideration in further design of structures with potential antioxidant properties.

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Background: Cancer is one of the leading causes of morbidity and mortality worldwide, with approximately 14 million new cases in 2012, with most of the clinically used drugs being ineffective. Methylxanthines have raised more interest in research on modifying their structure because of their diverse biological activity. In addition, the piperazine nucleus is one of the most important heterocycles exhibiting remarkable pharmacological activities. Methods: The structure of the obtained compounds was characterized and elucidated by IR, 1H and 13C NMR and LCMS spectral analysis. The purity of the substances was proven by corresponding melting points and elemental analysis. The antioxidant activity was evaluated by four common methods – DPPH, ABTS, FRAP and lipid peroxidation assay. The cytotoxic effects of the tested series were evaluated using the standard MTT-dye reduction assay on three tumour cell lines. Results: A series of new xanthine derivatives comprising an arylpiperazine moiety at N1 were synthesized. The cytotoxicity against human T-cell leukemia cell SKW-3, human acute myeloid leukemia HL-60 and human Bcell precursor leukemia cell REH was evaluated. The relationship between the structure and citotoxicity of the compounds was investigated by quantitative structure-activity relationship (QSAR) analysis and the important structural parameters were drawn. Conclusion: The highest antioxidant activity was demonstrated by compound 6c. The highest cytotoxic effect was observed for compound 6f. It was found that cytotoxicity against SKW-3 depends on the electron density distribution in the structures. Branching of the molecular skeleton and introduction of heteroatoms like fluorine and sulfur in the structures also significantly improved the antiproliferative activity of the compounds.

Background: Cannabidiol (CBD) is the main, physiologically active, but psycho-inactive constituent of the glandular hairs of Cannabis sativa. CBD exhibits diverse pharmacological activities and it is used as anticonvulsant, sedative and hypnotic agent. Other biological properties shown by CBD are antipsychotic, anti-inflammatory and neuroprotective. Objective: The aim of this study is to develop, validate and apply high performance liquid chromatography (HPLC/DAD) method with diode array detection for identification and assay of CBD in food supplements obtained by different types of extraction and purification. Method: HPLC method with isocratic elution using column C18 ODS, 250 x 4.6, 100 A, 5 μm, mobile phase - mixture of acetonitrile and water in ratio 80:20v/v, flow rate of 1.0 ml/min and DAD detection at 220 nm. Results: The method was developed and validated according to European Pharmacopoeia and International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH). For the purposes analytical parameters repeatability, linearity, accuracy, LOD, LOQ, specificity and system suitability test were studied. The developed method was successfully applied on a series of food supplements containing CBD. Conclusion: The developed method is of practical importance for determination of purity, identification and assay tests of food supplements containing CBD extract in accordance with EU regulation concerning food authorizations because it is useful for analytical tests for identification, purity determination and assay of products containing CBD extract and could serve as part of the testing process in the pharmaceutical industry.

Human neutrophil peptides (HNPs, alpha-defensins) are a group of six defensins being considered as new antimicrobial drugs because of their multifunctional efficiency against bacteria, viruses and fungi. Regardless of the unique biological properties, alphadefensins are unstable compounds and their activity depends on many physical and chemical factors as well as on the kind of the used cultivation media. This leads to research difficulties and obstructions in their therapeutic application. The purpose of this study was to determine antibacterial activity of alpha-defensin 2 dissolved in pharmacopeia buffers and in parallel to develop selective and accurate analytical tests for identification and assay of alpha-defensin 2 in the course of study. The antibacterial effect of alpha-defensin 2 was determined against the strain Escherichia coli (ATCC 25922). It was found that 10 mg/L of Human neutrophil peptide-2 (HNP-2, alpha-defensin 2) dissolved in pH 9.0 buffer caused 90% inhibition of the bacterial respiratory activity. This buffer was considered as a suitable environment for deploying the antibacterial activity of the alpha-defensin. A selective MS analysis method for the identification of alpha-defensin 2 in sample mixtures was developed. Also, the HPLC method with alternative selectivity was elaborated for identification and assay of mixtures containing alpha-defensin 2 and aminoacids in Mueller Hinton broth. The procedure includes development of system suitability test determination.