| 1. |
- Bohlin, Lars, et al.
(författare)
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Podophyllotoxin derivatives : drug discovery and development
- 1996
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Ingår i: Drug Discovery Today. - : Elsevier. - 1359-6446 .- 1878-5832. ; 1:8, s. 343-351
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Forskningsöversikt (refereegranskat)abstract
- The exploration and exploitation of podophyllin formulations provide an example of how a plant extract with established ethnomedical use, but also causing toxicity, can provide a basis for new drug discovery and development. Applications and potential applications include the treatment of venereal warts, psoriasis, rheumatoid arthritis, malaria and Alzheimer's disease. This review addresses the history and pharmacological action of these natural products and outlines the preclinical development and clinical trials of drugs in the pipeline and with marketing approval.
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| 2. |
- Bruhn, Jan G., et al.
(författare)
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Molecular Pharmacognosy : an explanatory model
- 1997
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Ingår i: Drug Discovery Today. - : Elsevier. - 1359-6446 .- 1878-5832. ; 2:6, s. 243-246
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Forskningsöversikt (refereegranskat)abstract
- Increased interest in the study of natural products as potential drugs and rapidly changing research strategies are driving us to reassess the role of pharmacognosy in the wider context of pharmaceutical research. The authors propose a new definition and an explanatory model of modern pharmacognosy that can be used as a theoretical foundation for future development of this classical branch of the life sciences.
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| 3. |
- El-Seedi, Hesham, et al.
(författare)
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Biosynthesis, natural sources, dietary intake, pharmacokinetic properties, and biological activities of hydroxycinnamic acids
- 2012
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Ingår i: Journal of Agricultural and Food Chemistry. - : American Chemical Society (ACS). - 0021-8561 .- 1520-5118. ; 60:44, s. 10877-10895
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Forskningsöversikt (refereegranskat)abstract
- Hydroxycinnamic acids are the most widely distributed phenolic acids in plants. Broadly speaking, they can be defined as compounds derived from cinnamic acid. They are present at high concentrations in many food products, including fruits, vegetables, tea, cocoa, and wine. A diet rich in hydroxycinnamic acids is thought to be associated with beneficial health effects such as a reduced risk of cardiovascular disease. The impact of hydroxycinnamic acids on health depends on their intake and pharmacokinetic properties. This review discusses their chemistry, biosynthesis, natural sources, dietary intake, and pharmacokinetic properties.
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| 4. |
- El-Seedi, Hesham R., et al.
(författare)
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Recent insights into the biosynthesis and biological activities of natural xanthones
- 2010
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Ingår i: Current Medicinal Chemistry. - : Bentham Science Publishers Ltd.. - 0929-8673 .- 1875-533X. ; 17:9, s. 854-901
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Forskningsöversikt (refereegranskat)abstract
- This review focuses on recent advances in our understanding of the complex biosynthetic pathways and diverse biological activities of naturally occurring xanthones. The biosynthesis section covers studies published from 1989 to 2008 on xanthone production in plants and fungi, while the bioactivity review presents tabulated activities of more than 250 xanthones described in studies published from 2001 to 2008, together with structural information and indications of their wide-ranging potential uses as pharmacological tools. A large number of relevant papers have been published on these subjects (128 cited here), illustrating the diversity of the xanthones and their possible uses.
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| 5. |
- Muigg, Patrik, et al.
(författare)
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In silico comparison of marine, terrestrial and synthetic compounds using ChemGPS-NP for navigating chemical space
- 2013
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Ingår i: Phytochemistry Reviews. - : Springer Science and Business Media LLC. - 1568-7767 .- 1572-980X. ; 12:3, s. 449-457
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Forskningsöversikt (refereegranskat)abstract
- Nature represents a vast source of chemical diversity, which is supposed to cover broader areas of chemical space than synthetically obtained substances typical of medicinal chemistry. With regard to drug discovery from nature, the terrestrial environment has been the most and longest studied source, while the investigation of compounds produced by marine organisms is still in its infancy. With the objective of demonstrating the enormous chemical diversity of nature, in particular that of the marine environment, we used the chemical space navigation tool ChemGPS-NP to compare sets of marine, terrestrial and synthetic compounds with respect to physico-chemical properties and their occupation of the biologically relevant chemical space. Despite considerable overlap, the three datasets clearly differ from each other by occupying and extending into different, specific, regions in chemical space. Synthetic compounds are e.g. comparably small, with some of them being highly flexible, while marine and terrestrial products are larger and characterised by higher and lower molecular flexibility, respectively, with increasing size. Moreover, the three datasets differ to some degree in polarity, aromaticity and heteroatom content. Taken together, ChemGPS-NP has been proven to be a useful tool for navigating large volumes of biologically relevant chemical space. In this study we demonstrated the chemical uniqueness and differences of large sets of natural products, with particular emphasis on marine substances. The hence de-veiled differences further underline the relevance of natural products, of both marine and terrester origin, for future drug discovery.
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| 6. |
- Strömstedt, Adam A., et al.
(författare)
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Bioassays in Natural Product Research : Strategies and Methods in the Search for Anti-inflammatory and Antimicrobial Activity
- 2014
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Ingår i: Phytochemical Analysis. - : Wiley. - 0958-0344 .- 1099-1565. ; 25:1, s. 13-28
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Forskningsöversikt (refereegranskat)abstract
- Introduction: Identifying bioactive molecules from complex biomasses requires careful selection and execution of relevant bioassays in the various stages of the discovery process of potential leads and targets.Objective: The aim of this review is to share our long-term experience in bioassay-guided isolation, and mechanistic studies, of bioactive compounds from different organisms in nature with emphasis on anti-inflammatory and antimicrobial activity.Methods: In the search for anti-inflammatory activity, in vivo and in vitro model combinations with enzymes and cells involved in the inflammatory process have been used, such as cyclooxygenases, human neutrophils and human cancer cell lines. Methods concerning adsorption and perforation of bacteria, fungi, human cells and model membranes, have been developed and optimised, with emphasis on antimicrobial peptides and their interaction with the membrane target, in particular their ability to distinguish host from pathogen.Results: A long-term research has provided experience of selection and combination of bioassay models, which has led to an increased understanding of ethnopharmacological and ecological observations, together with in-depth knowledge of mode of action of isolated compounds.Conclusion: A more multidisciplinary approach and a higher degree of fundamental research in development of bioassays are often necessary to identify and to fully understand the mode of action of bioactive molecules with novel structure-activity relationships from natural sources. Selection and execution of relevant bioassays are critical in the various stages of the discovery process of potential drug leads and targets from natural sources. The aim of this review is to share our long-term experience in bioassay-guided isolation of bioactive compounds from different organisms in nature with emphasis on anti-inflammatory and antimicrobial activity. We conclude that an increased multidisciplinary approach and a higher degree of fundamental research in development of bioassays are essential to discover complex structure-activity relationships.
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| 7. |
- Tulp, Martin, et al.
(författare)
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Food for thought
- 2006
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Ingår i: Drug Discovery Today. - : Elsevier BV. - 1359-6446 .- 1878-5832. ; 11:23-24, s. 1115-1121
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Forskningsöversikt (refereegranskat)abstract
- Do certain kinds of food contain pharmacologically active substances in concentrations that are high enough to have druglike effects when consumed? Are biologically active compounds in food indicative of therapeutic value? Is traditional drug development suitable for testing the merits of food? Is it ethical to test food as a drug on patients? Will dietary disease management remain a pipedream? Is it a fact or fantasy that the Mediterranean diet is beneficial to health? Is a vegetarian diet an elimination therapy, or one of supplementation? What can be learned from animals? Are humans losing the capability of listening to their bodies? In this review, we will address these questions-providing food for thought.
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| 8. |
- Tulp, Martin, et al.
(författare)
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Unconventional natural sources for future drug discovery
- 2004
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Ingår i: Drug Discovery Today. - 1359-6446 .- 1878-5832. ; 9:10, s. 450-458
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Forskningsöversikt (refereegranskat)abstract
- ‘There are more things between heaven and earth…’ Despite the progress of science during the past four centuries, Shakespeare's words did not lose their actuality. Knowledge about the etiology of diseases is still limited, and for many life-threatening illnesses no effective treatments exist. Nature always has been a valuable source of drugs and, despite the unprecedented opportunities afforded by medicinal chemistry, continues to deliver lead compounds. Traditionally, research on natural sources was focused on terrestrial plants and microorganisms. More recently, however, organisms of marine origin are also being investigated. Here, the possibilities of unconventional and hardly explored sources are discussed.
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| 9. |
- Wang, Likui, et al.
(författare)
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Antioxidative Dietary Compounds Modulate Gene Expression Associated with Apoptosis, DNA Repair, Inhibition of Cell Proliferation and Migration
- 2014
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Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1661-6596 .- 1422-0067. ; 15:9, s. 16226-16245
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Forskningsöversikt (refereegranskat)abstract
- Many dietary compounds are known to have health benefits owing to their antioxidative and anti-inflammatory properties. To determine the molecular mechanism of these food-derived compounds, we analyzed their effect on various genes related to cell apoptosis, DNA damage and repair, oxidation and inflammation using in vitro cell culture assays. This review further tests the hypothesis proposed previously that downstream products of COX-2 (cyclooxygenase-2) called electrophilic oxo-derivatives induce antioxidant responsive elements (ARE), which leads to cell proliferation under antioxidative conditions. Our findings support this hypothesis and show that cell proliferation was inhibited when COX-2 was down-regulated by polyphenols and polysaccharides. Flattened macrophage morphology was also observed following the induction of cytokine production by polysaccharides extracted from viili, a traditional Nordic fermented dairy product. Coix lacryma-jobi (coix) polysaccharides were found to reduce mitochondrial membrane potential and induce caspase-3- and 9-mediated apoptosis. In contrast, polyphenols from blueberries were involved in the ultraviolet-activated p53/Gadd45/MDM2 DNA repair system by restoring the cell membrane potential. Inhibition of hypoxia-inducible factor-1 by saponin extracts of ginsenoside (Ginsen) and Gynostemma and inhibition of S100A4 by coix polysaccharides inhibited cancer cell migration and invasion. These observations suggest that antioxidants and changes in cell membrane potential are the major driving forces that transfer signals through the cell membrane into the cytosol and nucleus, triggering gene expression, changes in cell proliferation and the induction of apoptosis or DNA repair.
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