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Synthesis of Novel Anti‐inflammatory Psoralen Derivatives ‐ Structures with Distinct Anti‐Inflammatory Activities
Author(s) -
Timonen Juri M.,
Vuolteenaho Katriina,
Leppänen Tiina,
Nieminen Riina M.,
Aulaskari Paula,
Jänis Janne,
Vainiotalo Pirjo,
Moilanen Eeva
Publication year - 2018
Publication title -
journal of heterocyclic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.321
H-Index - 59
eISSN - 1943-5193
pISSN - 0022-152X
DOI - 10.1002/jhet.3318
Subject(s) - chemistry , psoralen , anti inflammatory , furan , substituent , stereochemistry , coumarin , intramolecular force , pyrone , combinatorial chemistry , organic chemistry , pharmacology , dna , biochemistry , medicine
As a continuum to our work with coumarins, 12 psoralens were synthesized and evaluated for their anti‐inflammatory activity. Psoralens were prepared in three steps; at first, 7‐hydroxycoumarins were synthesized by von Pechmann condensation and then converted to 7‐(2‐oxopropoxy)coumarins. In the final step, a fused furan ring was introduced in an intramolecular ring‐formation reaction. Based on a SciFinder search, two out of the 12 synthesized psoralen derivatives (compounds 9 and 12 ) were found to be novel. The derivatives displayed anti‐inflammatory activity by suppressing iNOS and IL‐6 expression, but their mechanism of action seemed to be dependent on the substitution. Compound 6 with propyl side chain inhibited NF‐κB mediated transcription, while compound 10 with a phenyl substituent down‐regulated iNOS expression in a posttranscriptional manner. The results introduce psoralen derivatives as promising anti‐inflammatory compounds with potential for treatment of conditions involving iNOS and/or IL‐6‐mediated adverse responses.