During the last decade, we have studied the anti-inflammatory effects of different series of coumarin derivatives. We started by studying the inhibitory activity of 7-hydroxycoumarins and 7-(2-oxoalkoxy)coumarins on the production of both nitric oxide (NO) and interleukine-6 (IL-6) and on the expression of inductive nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Experiments were conducted in collaboration with The Immunopharmacology research group at the School of Medicine in the University of Tampere. In our studies, we found coumarins mechanism of action for inhibition of NO production to be due to inactivation of the NF-kB pathway.[1,2]
Results, published in 2018, strongly indicated that the mechanisms of anti-inflammatory activity of 4′-methyl psoralens are dependent on the size of the side chain in position 4. Our results suggest that the mechanism of action of the psoralens bearing an aliphatic substituent in position 4 is similar to the NF-kB pathway inactivation by 7-hydroxycoumarins. However, a phenyl ring in position 4 seems to change the mechanistic pathway of NF-kB inactivation to post-transcriptional modification of iNOS mRNA.[3]
[1] Timonen,
J. M., et al. (2009), Eur. J. Med. Chem., 46(9), 3845-3850.
[2] Timonen, J., et al. (2015), J. Het. Chem., 52(5),
1286-1295.
[3] Timonen, J. M., et al. (2018), J. Het. Chem., 55(11),
2590-2597.