Structure, uses and history of Coumarins

Coumarins, also known as 1-bezopyran-2-ones or 2H-chromen-2-ones are a group of natural products. Structurally they are closely related to many plant deroved phenolic compounds such as flavonoids and chromenes. Coumarins are secondasry metabolites of plants biosynthetised via Shikimate pathway from cinnamic acid. Coumarins has shown versatile pharmacological effects as anticoagulants, anti-inflammatory agents, anti-HIV agents etc. as well as use in different techno-chemical applications, e.g. laser dyes because of theri photochemical properties. One of the best known coumarin based drug in market is Warfarin(R), an anti-coagulant used to thin the patients blood.

One of the most important coumarin derivative has long been 7-hydroxy coumarin. It was found in mid 19th Century, but the first solid proof of the structure of coumarin scaffold is from early 20th Centuiry. Until now, there has been tens of thousands publications of properties, biodistribution, usage and preparation of different natural and non-naturalcoumarin derivatives.

One of the most interesting biological property of coumarins is their anti-inflammatory activity. Research on their anti-inflammatory activy has shown their potency to suppres release of pro-inflammatory cytokines, production of nitric oxide (NO) and also expression of indcible nitric oxide synthase (iNOS). Recent studies has also proposed them to act both by blocking NF-kB pahway and by some postrtranscriptional pathway.

Our research on Coumarins

Synthesis of Coumarins

In our group, we are continuosly developing different coumarin scaffolds. Our current research on method development aims to more eco-friendly and more efficient methods to produce substituted coumarins. In the research we are using the state-of-the-art methods, like micriwave assisted synthesis. The research serves all fields of our coumarin researc.

TRPA1 Antagonists

Our group started research on TRPA1 ion chanel in 2017. Our goal is to design, synthetize and screen coumarin based antagonists for TRPA1, an ion chanel that plays important role in pain sensation and neuropathic pain. The project is collaboration with the Immunopharmacology Research Group ( Tampere University) and the Sirtuin Research group (University of Eastern Finland).

Mass Spectrmetry of Coumarins

As coumarins are secondary metabolites of plants, plant extracts, herbal medicines and infusions contain various coumarins. Identification of active compounds of these folk medicines may give a good starting point for drug development. Dr Timonen has long worked to develope tools for identification of structurally different coumarin derivatives with freagmentation mass spectrometry.

Anti-inflammatory Coumarins

Dr Timonen started to work wih anti-inflammatory coumarins in 2000 and his doctora thesis was entitled “Synthesis, characterization and anti-inflammatory effects of substituted coumarine derivatives ” In our group, we continue the research of anti-inflammatory effects of coumarins. At the moment we have two ongoing collaborations in the field.

Metabolism of Coumarins

Our group started to collaborate with Assosiate Professor Risto Juvonen and the Toxicology Research Group of UEF in 2017. The group has been interested in metabolism and glucuronidation of 7-Hydroxycoumarins a long time, and they have a solid experience on metabolic research. Understanding the metabolic behavior of chemicals is in a key role in drug design.