Synthesis of new azulene derivatives and study of their effect on lipid peroxidation and lipoxygenase activity.
The relationship between free radicals and acute or chronic inflammation has been well established. We have previously reported the significant antioxidant activity of the natural azulene derivatives chamazulene and guaiazulene. Furthermore, some synthetic azulene analogues have been found to possess anti-inflammatory activity. In this investigation we report the synthesis of five 3-alkyl or 3-(hydroxy)alkylazulene-1-carboxylic acids and esters, from tropolone, via the corresponding furanone. The synthesised compounds were tested for their effect on the peroxidation of rat hepatic microsomal membrane lipids, applying the 2-thiobarbituric acid test. Their anti-inflammatory activity was evaluated in vitro by the offered inhibition of soybean lipoxygenase. All the tested molecules were found to inhibit lipid peroxidation by 100% at 1 mM. They were also found to considerably inhibit lipoxygenase activity. The above results are discussed in relation to the structure and physicochemical properties of the examined azulene derivatives.
Department of Pharmaceutical Chemistry, School of Pharmacy, Aristotelian University of Thessaloniki, Greece. rekka@pharm.auth.gr
Eleni
E
Rekka
Michael
M
Chrysselis
Ioanna
I
Siskou
Angeliki
A
Kourounakis
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000494:pharmacology*; D052176:Azulenes; D003508:Cycloheptanes / Q000138:chemical synthesis* / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000138:chemical synthesis* / Q000494:pharmacology*; D007202:Indicators and Reagents; D015227:Lipid Peroxidation / Q000187:drug effects*; D016859:Lipoxygenase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D051381:Rats; D011916:Rats, Inbred F344; D013055:Spectrophotometry, Infrared; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D052176:Azulenes; D003508:Cycloheptanes; D016166:Free Radical Scavengers; D007202:Indicators and Reagents; D016859:Lipoxygenase Inhibitors; D017392:Thiobarbituric Acid Reactive Substances; C005525:azulene