New methods for the laboratory-scale synthesis of coumarin-based drugs were developed in a recent study completed at the University of Eastern Finland. In his doctoral thesis, Lic. Phil. Juri Timonen also developed new analytical methods for the fast identification of natural and non-natural coumarins. A few of the synthesised coumarins were also found to inhibit some specific reactions generally associated with inflammation.
Coumarin is an aromatic compound, naturally occurring in many plants. In foodstuffs coumarins are found especially in cinnamon and tonka beans. The bioactivity of coumarins has been utilised in many drugs; for example, coumarins exhibit anti-inflammatory as well as anticoagulant activities. One of the best-known drugs based on a coumarin scaffold is Marewan®, a commercial blood anticoagulant.
The study made considerable improvements to the decades-old synthesis method of coumarins. Most of the previous methods are based on heating of the starting material with a strong acid, but the newly developed method also works at room temperature. The improvements also lower the production costs, since the final products are easier to purify.
A commonly used inflammation model showed that some of the synthesised coumarins remarkably reduced the production of typical signalling molecules, such as nitric oxide synthase and nitric oxide itself, which are usually linked to inflammation. In this assay, a murine cell line from mice imitated the inflammatory response. The results also revealed one of the pathways in which coumarins act. Understanding of this pathway and data on nearly 50 tested coumarins may help in the development of future anti-inflammatory drugs for chronic inflammation diseases such as asthma and rheumatoid arthritis.
Developing new analytical methods for natural and non-natural compounds is important in the screening of natural products with biological activity as well as in studies of drug metabolism. By using a mass spectrometric method developed in this study, even very similar compounds can be distinguished and characterized based on their fragmentation during the analysis.
A fragmentation pattern for a given molecule obtained by a mass spectrometer resembles a fingerprint; it is dependent only on the structure of the molecule and two non-identical molecules produce different patterns. The study revealed some interesting details on the fragmentation of synthesized coumarins. This knowledge can be used in the future to predict fragmentation of novel coumarins.
The findings were originally published in European Journal of Medical Chemistry, European Journal of Mass Spectrometry, and Rapid Communications in Mass Spectrometry.
Explore further: Study on coumarin in cinnamon and cinnamon-based products
More information: Timonen, J. M.; Nieminen, R. M.; Sareila, O.; Goulas, A.; Moilanen, L. J.; Haukka, M.; Vainiotalo, P.; Moilanen, E.; Aulaskari, P. H.; Synthesis and anti-inflammatory effects of a series of novel 7-hydroxycoumarin derivatives, Eur. J. Med. Chem. 2011, 46, pp. 3845-50.
Timonen, J.; Aulaskari, P.; Hirva, P.; Vainiotalo, P.; Negative ion electrospray ionization mass spectrometry and computational studies on substituted 7-hydroxycoumarins, Eur. J. Mass Spectrom. 2009, 15, pp. 595-603.
Timonen, J.; Romppanen, R.; Aulaskari, P.; Jänis, J.; Low-energy collision induced dissociation tandem mass spectrometry of 7-acetonyloxycoumarins, Rapid Commun. Mass Spectrom. 2013, 27, pp. 2665-2675.
Medical Xpress on facebook
Related Stories
Study on coumarin in cinnamon and cinnamon-based products
May 08, 2013
Many kinds of cinnamon, cinnamon-flavored foods, beverages and food supplements in the United States use a form of the spice that contains high levels of a natural substance that may cause liver damage in ...
Researchers identify molecules with interesting anti-clotting properties
Nov 08, 2007
Virginia Commonwealth University researchers have discovered a new mechanism to inhibit key enzymes that play a major role in clotting disorders, which could lead to novel therapies to treat clots in the lungs ...
Inflammatory on and off switch identified for allergic asthma and COPD
Aug 01, 2013
Japanese researchers have made a new step toward understanding why—and how to stop—runaway inflammation for both chronic obstructive pulmonary disorder (COPD) and allergic asthma. In a new report appearing in the August ...
Sniffing out fake perfumes
Sep 25, 2013
Scientists at EPFL have designed a quick method for detecting counterfeit perfumes, and have tested it on major brands like Givenchy, Hermes and D&G.
Target for new Rx class for inflammatory disorders discovered
Oct 03, 2013
Research led by Charles Nichols, PhD, Associate Professor of Pharmacology at LSU Health Sciences Center New Orleans, describes a powerful new anti-inflammatory mechanism that could lead to the development of new oral medications ...
Recommended for you
Researchers identify how body clock affects inflammation
Nov 07, 2013
UT Southwestern Medical Center researchers report that disrupting the light-dark cycle of mice increased their susceptibility to inflammatory disease, indicating that the production of a key immune cell is ...
Research identifies potential link between macrophage response and chronic inflammatory disease
Nov 07, 2013
Tiny cells which have the ability to trigger the body's immune responses could be crucial to research into a number of chronic medical conditions, scientists have suggested.
Few parents use kids' asthma meds correctly, study finds
Nov 01, 2013
(HealthDay)—Most adults who help children take inhaled asthma medications don't know all of the steps involved for their proper use, new research finds.
Gum disease treated by bringing needed immune cells to inflamed tissue
Nov 01, 2013
The red, swollen and painful gums and bone destruction of periodontal disease could be effectively treated by beckoning the right kind of immune system cells to the inflamed tissues, according to a new animal study conducted ...
Itch maintains regulatory T cell stability
Oct 26, 2013
Regulatory T cells (Tregs) function to suppress immune responses of other cells, and their dysfunction has been associated with development of immune disorders. Recent studies suggest that Tregs maintain plasticity even after ...
Hope of new treatment for severe asthma patients
Oct 25, 2013
New research from Japan brings hope of a new treatment for asthma patients resistant to corticosteroids. In a study published today in the journal Nature Communications, researchers from the RIKEN Center ...
User comments
© Medical Xpress 2011-2013, Phys.org network
New methods for the laboratory-scale synthesis of coumarin-based drugs were developed in a recent study completed at the University of Eastern Finland. In his doctoral thesis, Lic. Phil. Juri Timonen also developed new analytical methods for the fast identification of natural and non-natural coumarins. A few of the synthesised coumarins were also found to inhibit some specific reactions generally associated with inflammation.
Coumarin is an aromatic compound, naturally occurring in many plants. In foodstuffs coumarins are found especially in cinnamon and tonka beans. The bioactivity of coumarins has been utilised in many drugs; for example, coumarins exhibit anti-inflammatory as well as anticoagulant activities. One of the best-known drugs based on a coumarin scaffold is Marewan®, a commercial blood anticoagulant.
The study made considerable improvements to the decades-old synthesis method of coumarins. Most of the previous methods are based on heating of the starting material with a strong acid, but the newly developed method also works at room temperature. The improvements also lower the production costs, since the final products are easier to purify.
A commonly used inflammation model showed that some of the synthesised coumarins remarkably reduced the production of typical signalling molecules, such as nitric oxide synthase and nitric oxide itself, which are usually linked to inflammation. In this assay, a murine cell line from mice imitated the inflammatory response. The results also revealed one of the pathways in which coumarins act. Understanding of this pathway and data on nearly 50 tested coumarins may help in the development of future anti-inflammatory drugs for chronic inflammation diseases such as asthma and rheumatoid arthritis.
Developing new analytical methods for natural and non-natural compounds is important in the screening of natural products with biological activity as well as in studies of drug metabolism. By using a mass spectrometric method developed in this study, even very similar compounds can be distinguished and characterized based on their fragmentation during the analysis.
A fragmentation pattern for a given molecule obtained by a mass spectrometer resembles a fingerprint; it is dependent only on the structure of the molecule and two non-identical molecules produce different patterns. The study revealed some interesting details on the fragmentation of synthesized coumarins. This knowledge can be used in the future to predict fragmentation of novel coumarins.
The findings were originally published in European Journal of Medical Chemistry, European Journal of Mass Spectrometry, and Rapid Communications in Mass Spectrometry.
Explore further: Study on coumarin in cinnamon and cinnamon-based products
More information: Timonen, J. M.; Nieminen, R. M.; Sareila, O.; Goulas, A.; Moilanen, L. J.; Haukka, M.; Vainiotalo, P.; Moilanen, E.; Aulaskari, P. H.; Synthesis and anti-inflammatory effects of a series of novel 7-hydroxycoumarin derivatives, Eur. J. Med. Chem. 2011, 46, pp. 3845-50.
Timonen, J.; Aulaskari, P.; Hirva, P.; Vainiotalo, P.; Negative ion electrospray ionization mass spectrometry and computational studies on substituted 7-hydroxycoumarins, Eur. J. Mass Spectrom. 2009, 15, pp. 595-603.
Timonen, J.; Romppanen, R.; Aulaskari, P.; Jänis, J.; Low-energy collision induced dissociation tandem mass spectrometry of 7-acetonyloxycoumarins, Rapid Commun. Mass Spectrom. 2013, 27, pp. 2665-2675.
Medical Xpress on facebook
Related Stories
Study on coumarin in cinnamon and cinnamon-based products
May 08, 2013
Many kinds of cinnamon, cinnamon-flavored foods, beverages and food supplements in the United States use a form of the spice that contains high levels of a natural substance that may cause liver damage in ...
Researchers identify molecules with interesting anti-clotting properties
Nov 08, 2007
Virginia Commonwealth University researchers have discovered a new mechanism to inhibit key enzymes that play a major role in clotting disorders, which could lead to novel therapies to treat clots in the lungs ...
Inflammatory on and off switch identified for allergic asthma and COPD
Aug 01, 2013
Japanese researchers have made a new step toward understanding why—and how to stop—runaway inflammation for both chronic obstructive pulmonary disorder (COPD) and allergic asthma. In a new report appearing in the August ...
Sniffing out fake perfumes
Sep 25, 2013
Scientists at EPFL have designed a quick method for detecting counterfeit perfumes, and have tested it on major brands like Givenchy, Hermes and D&G.
Target for new Rx class for inflammatory disorders discovered
Oct 03, 2013
Research led by Charles Nichols, PhD, Associate Professor of Pharmacology at LSU Health Sciences Center New Orleans, describes a powerful new anti-inflammatory mechanism that could lead to the development of new oral medications ...
Recommended for you
Researchers identify how body clock affects inflammation
Nov 07, 2013
UT Southwestern Medical Center researchers report that disrupting the light-dark cycle of mice increased their susceptibility to inflammatory disease, indicating that the production of a key immune cell is ...
Research identifies potential link between macrophage response and chronic inflammatory disease
Nov 07, 2013
Tiny cells which have the ability to trigger the body's immune responses could be crucial to research into a number of chronic medical conditions, scientists have suggested.
Few parents use kids' asthma meds correctly, study finds
Nov 01, 2013
(HealthDay)—Most adults who help children take inhaled asthma medications don't know all of the steps involved for their proper use, new research finds.
Gum disease treated by bringing needed immune cells to inflamed tissue
Nov 01, 2013
The red, swollen and painful gums and bone destruction of periodontal disease could be effectively treated by beckoning the right kind of immune system cells to the inflamed tissues, according to a new animal study conducted ...
Itch maintains regulatory T cell stability
Oct 26, 2013
Regulatory T cells (Tregs) function to suppress immune responses of other cells, and their dysfunction has been associated with development of immune disorders. Recent studies suggest that Tregs maintain plasticity even after ...
Hope of new treatment for severe asthma patients
Oct 25, 2013
New research from Japan brings hope of a new treatment for asthma patients resistant to corticosteroids. In a study published today in the journal Nature Communications, researchers from the RIKEN Center ...
User comments
© Medical Xpress 2011-2013, Phys.org network
No comments:
Post a Comment