Hassan S.T.S.,University of Veterinary And Pharmaceutical Sciences Brno |
Zemlicka M.,University of Veterinary Medicine in Kosice
Archiv der Pharmazie | Year: 2016
Inhibition of the metalloenzyme urease has important pharmacologic applications in the field of antiulcer and antigastric cancer agents. Urease is involved in many serious infections caused by Helicobacter pylori in the gastric tract as well as by Proteus and related species in the urinary tract. Although numerous studies have described several novel urease inhibitors (UIs) used for the treatment of gastric and urinary infections, all these compounds have exhibited severe side effects, toxicity, and instability. Therefore, to overcome such problems, it is necessary to search for new sources of UIs, such as natural products, that provide reduced side effects, low toxicity, greater stability, and bioavailability. As limited studies have been conducted on plant-derived UIs, this paper aims to highlight and summarize the most promising compounds isolated and identified from plants, such as terpenoids, phenolic compounds, alkaloids, and other substances with inhibitory activities against plant and bacterial ureases; these are in vitro and in vivo studies with an emphasis on structure–activity relationship studies and types of inhibition that show high and promising levels of anti-urease activity. This will aid medicinal chemists in the design and synthesis of novel and pharmacologically potent UIs useful for the development of antiulcer drugs. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Zelova H.,University of Veterinary And Pharmaceutical Sciences Brno |
Hosek J.,University of Veterinary And Pharmaceutical Sciences Brno
Inflammation Research | Year: 2013
Introduction: Inflammation is a very important part of innate immunity and is regulated in many steps. One such regulating step is the cytokine network, where tumor necrosis factor α (TNF-α) plays one of the most important roles. Methods: A PubMed and Web of Science databases search was performed for studies providing evidences on the role of TNF-α in inflammation, apoptosis, and cancer. Results and Conclusion: This review concisely summarizes the role of this pro-inflammatory cytokine during inflammation. It is focused mainly on TNF-α intracellular signaling and its influence on the typical inflammatory features in the organism. Being one of the most important pro-inflammatory cytokines, TNF-α participates in vasodilatation and edema formation, and leukocyte adhesion to epithelium through expression of adhesion molecules; it regulates blood coagulation, contributes to oxidative stress in sites of inflammation, and indirectly induces fever. The connection between TNF-α and cancer is mentioned as well. © 2013 Springer Basel.
Vranikova B.,University of Veterinary And Pharmaceutical Sciences Brno |
Gajdziok J.,University of Veterinary And Pharmaceutical Sciences Brno
Acta Pharmaceutica | Year: 2013
Many modern drugs are poorly water soluble substances, which causes difficulties in the development of solid dosage forms with sufficient bioavailability. Preparation of liquisolid systems (LSS) is a novel technique for improving solubility, dissolution and bioavailability of such drugs. The basic principle of LSS preparation is conversion of the drug in liquid state into a free-flowing, compressible, dry powder through its absorption into suitable excipients-porous carriers (aluminometasilicates, microcrystalline cellulose), subsequently coated with material having high absorption capacity (silicon dioxide commonly known as colloidal silica). LSS exhibit advantages such as lower production costs compared to soft capsules, simple processing and enhanced drug release. The main benefit is higher bioavailability of the liquid drug, caused by a large surface area available for absorption. The article tries to clarify specific aspects connected with the formulation of LSS: Properties of excipients (surface area, absorption capacity), variables related to the processing (solubility, liquid load factor) and dosage form evaluation.
Smejkal K.,University of Veterinary And Pharmaceutical Sciences Brno
Ceska a Slovenska Farmacie | Year: 2014
Neuropathic pain is a syndrome comprising pain caused by a lesion or dysfunction of the nervous system, or resulting from lesions or diseases of the somatosensory system. Neuropathic pain is often connected with adverse effects of chemotherapy administered because of cancer, infiltration of the nervous tissue with cancer cells, neurodegeneration and diabetes mellitus. Disbalance in the production of various cytokines plays an important role in the pathogenesis of many of the diseases connected with neuropathies. These cytokines comprise in particular interleukins IL-1β, IL-15, and IL-6, tumour necrosis factors, and prostaglandins. The biochemistry of the production of cytokines is directed by nuclear factors, which affect the expression of the mRNA for the respective cytokines or enzymes metabolizing the cytokines. The main nuclear factor which regulates the expression of cytokines is NF-κB. Because of insufficient effectiveness or adverse effects of the pharmacological treatment of peripheral neuropathy, many patients seek supportive or adjuvant therapy. Natural compounds which modulate the production of inflammatory cytokines may reduce the symptoms of neuropathies. Many natural phenolic compounds belong to substances affecting the activity of NF-κB and consequently the activity of cytokines which are regulated by this substance. The aim of this mini-review is to present information about three natural phenols which are potentially usable for the treatment of neuropathies: curcumin, resveratrol and mangiferin, and bring attention to the practical usability thereof. Curcumin and mangiferin are active constituents of plants; they have been used for centuries in traditional medicine. Biological effects of resveratrol have been known for a relatively short time; since the discovery of the so-called French paradox, attention has been focused on resveratrol. This summary includes particularly the information related to the influence on the activity of NF-κB, expression of anti-inflammatory cytokines, and antiradical activity, because imbalance between the creation and degradation of free radicals plays an important role in the activation of NF-κB and in inflammatory processes. It also briefly summarizes basic information concerning bioavailability, metabolism and practical application of the aforementioned substances. © 2014 Čes. slov. Farm.
Jampilek J.,University of Veterinary And Pharmaceutical Sciences Brno
Expert Opinion on Drug Discovery | Year: 2016
While it is true that only a small fraction of fungal species are responsible for human mycoses, the increasing prevalence of fungal diseases has highlighted an urgent need to develop new antifungal drugs, especially for systemic administration. This contribution focuses on the similarities between agricultural fungicides and drugs. Inorganic, organometallic and organic compounds can be found amongst agricultural fungicides. Furthermore, fungicides are designed and developed in a similar fashion to drugs based on similar rules and guidelines, with fungicides also having to meet similar criteria of lead-likeness and/or drug-likeness. Modern approved specific-target fungicides are well-characterized entities with a proposed structure-activity relationships hypothesis and a defined mode of action. Extensive toxicological evaluation, including mammalian toxicology assays, is performed during the whole discovery and development process. Thus modern agrochemical research (design of modern agrochemicals) comes close to drug design, discovery and development. Therefore, modern specific-target fungicides represent excellent lead-like structures/models for novel drug design and development. © 2015 2015 Taylor & Francis.
Agency: European Commission | Branch: H2020 | Program: CSA | Phase: ISIB-02-2014 | Award Amount: 2.09M | Year: 2015
Using the laying hen sector as a case study, we aim to demonstrate the potential for practice-driven innovation networks, supported by existing science and market-driven actors, to develop practical cost-effective solutions to sustainability challenges (objective 1). Multi-stakeholder networks will develop technical innovations to injurious pecking and the management of end-of-lay hens concerns based on practice, economics and scientific information (objective 2). A generic support package of communication web based tools, facilitation guides and on-line training programmes, designed to help science and market- driven actors, will then be available to support practice-driven innovation networks in other livestock sectors (objective 3). Finally we will develop policy recommendations that help realize the full potential of practice-driven innovation through multi stakeholder networks in livestock sectors (objective 4). This project will tackle four challenges associated with the need for grass-root innovation highlighted in the Horizon 2020 call; 1) legitimacy by robust practical and financial evaluation, 2) accessibility by communication between producers and existing innovation support actors, 3) connectivity by an industry-led dissemination strategy ensuring information about innovations are widely spread using existing communication tools and finally 4) sufficient resource by production of a support package and policy recommendations that facilitate better interaction of science-driven and practice-driven innovation. The success of this approach to the laying hen sector and other sectors will be evaluated by the ability of the network to encourage practice-led innovation, check the effectiveness of the innovation, ensure optimum use of scientific information, provide a route for traditional knowledge transfer when required, disseminate results of innovation to others and ensure that policy is informed by practice-led solutions.
Pavelcik F.,University of Veterinary And Pharmaceutical Sciences Brno
Journal of Applied Crystallography | Year: 2012
New methods have been developed for locating phosphate groups and nucleic acid bases in the electron density of RNA structures. These methods utilize a constrained real-space refinement of molecular fragments and a phased rotation-conformation-translation function. Real-space refinement has also contributed to the improvement of the bone/base method of RNA model building and to redesigning the method of building double helices in nucleic acid structures. This improvement is reflected in the increased accuracy of the model building and the ability to better distinguish between correct and false solutions. A program, RSR, was created, and the programs NUT, HEL and DHL were upgraded and organized into a program system, which is CCP4 oriented. Source codes will also be released. © 2012 International Union of Crystallography Printed in Singapore-all rights reserved.
Pazourek J.,University of Veterinary And Pharmaceutical Sciences Brno
Journal of Separation Science | Year: 2010
Calibration based on the "single-point calibration method", a simple exponential transformation of the response function of an evaporative light scattering detector was improved and applied to analysis of selected saccharides under hydrophilic interaction chromatography mode (a polar phase LiChrospher100 DIOL, mobile phase acetonitrile/water). The improved approach to the calibration procedure yielded a calibration curve with an excellent linearity (quality coefficient <5%). This quantitative evaluation of chromatograms of D-galactose suggested that not only anomers but even pyranose and furanose forms of the anomers could be resolved - the resulting calculations of abundance of the anomeric form strongly correlated with data from the literature obtainedmostly by NMR studies (analogous results were also obtained for D-arabinose, D-glucose, and D-mannose). Because of the rapid separation (retention time less than 10min), the observed correlation enabled to monitor anomeric conversion (mutarotation) of monosaccharides. © 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
Smejkal K.,University of Veterinary And Pharmaceutical Sciences Brno
Phytochemistry Reviews | Year: 2014
Prenylated flavonoids are a large group of compounds that combine a flavonoid skeleton with a lipophilic prenyl side-chain. The-side chain may be modified, especially by oxidation, and this variation contributes many structural possibilities. Combining the flavonoid skeleton with a lipophilicity of the prenyl side-chain gives the resultant great potential for biological activity. The cytotoxic activity of prenylated flavonoids has been reviewed with the aim of evaluating the potential of these compounds for further research. The search for activity has been restricted to from blood derived cells to limit the number of sources cited and get a more valuable comparison of the compounds. All sources touching on the potential toxicity of prenylated flavonoids on blood-cell lines in last 30 years of research have been cited in this review. The Sciencedirect, Web of Knowledge, Scifinder, and Reaxys databases were searched for reports, descriptions, and structural information prenylated flavonoids. A wide spectrum of cell lines, coupled with the presence and/or sometimes the absence of a standard cytotoxic compound used to compare effects made the evaluation of data more difficult. An attempt to identify each structure-activity relationships was made. Although the toxicity of the compounds described here does not usually reach the nanomolar range of concentration for leukemic cancer cell lines, the prenylated flavonoids may possess a strong advantage, in that they are relatively non-toxic to non-cancer cells. Some possible mechanisms of action for the cytotoxicic effect have also been described. © 2013 Springer Science+Business Media.
Jampilek J.,University of Veterinary And Pharmaceutical Sciences Brno
Current Medicinal Chemistry | Year: 2014
Antimicrobial diazanaphthalenes are indispensable in the treatment of various infections. The quinoxaline scaffold possesses unique physicochemical properties and provides a possibility of a great number of targeted modifications. Quinoxaline-based compounds have a wide range of promising biological properties; therefore a special attention is paid to them for research and designing of new drugs. In fact, quinoxaline can be considered as a privileged structure. The scaffold can be easily and rapidly constructed, which emphasizes the significance of this favourable structure. The review is focused on recently reported potential antibacterial, antimycobacterial, antifungal and antiprotozoal agents derived from the quinoxaline scaffold, their mechanism of action and structure-activity relationships. A brief classification of synthetic pathways of quinoxaline derivatives is provided too. © 2014 Bentham Science Publishers.