156006-10-9Relevant articles and documents
Synthesis of Novel Anti-inflammatory Psoralen Derivatives?-?Structures?with?Distinct?Anti-Inflammatory?Activities
Timonen, Juri M.,Vuolteenaho, Katriina,Lepp?nen, Tiina,Nieminen, Riina M.,Aulaskari, Paula,J?nis, Janne,Vainiotalo, Pirjo,Moilanen, Eeva
, p. 2590 - 2597 (2018/09/25)
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.
7-(2-Oxoalkoxy)coumarins: Synthesis and Anti-Inflammatory Activity of a Series of Substituted Coumarins
Timonen, Juri,Vuolteenaho, Katriina,Lepp?nen, Tiina,Nieminen, Riina,Moilanen, Eeva,Aulaskari, Paula,J?nis, Janne
, p. 1286 - 1295 (2015/10/06)
A series of 7-(2-oxoalkoxy)coumarins have been synthesized by conjugating substituted 7-hydroxycoumarins with different chloroketones. The anti-inflammatory properties of 7-(2-oxoalkoxy)coumarins were studied in LPS-induced inflammatory response in J774 macrophages. Western blot was used to determine the expression of iNOS and COX-2, NO was determined by measuring its metabolite nitrite by Griess reaction and IL-6 was measured by ELISA. Seventeen of the studied compounds inhibited NO and IL-6 production over 50% at 100 μM concentrations. IC50 values of the best inhibitors were 21 μM/24 μM (NO/IL-6) for compound 12 and 30 μM/10 μM (NO/IL-6) for compound 20. The main result was that the substitution with 7-(2-oxoalkoxy) group improved the anti-inflammatory properties of most of the investigated 7-hydroxycoumarins.
Synthesis and characterization of new methylpsoralens as potential photochemotherapeutic agents
Antonello,Zagotto,Mobilio,Marzano,Gia,Uriarte
, p. 277 - 280 (2007/10/02)
Three new psoralens with methyl groups on carbons involved in their reactive double bonds (compounds 9-11 in Scheme 1) were synthesized from the corresponding 7-hydroxycoumarins by cyclization of acetonyl derivatives of the latter in an alkaline medium. In preliminary tests, the new methyl-substituted psoralens exhibited considerable interaction in the dark with DNA, good photoreactivity against the macromolecule, and also interesting antiproliferative activity.