O-prenylated carbostyrils as a novel class of 15-lipoxygenase inhibitors: Synthesis, characterization, and inhibitory assessment

Catalyzed peroxidation of unsaturated lipid in animals and plants intimately is linked to the activity of 15-Lipoxygenase enzymes. Lipoxygenases (LOXs) are well known to play an important role in many acute and chronic syndromes such as inflammation, asthma, cancer, and allergy. In this study, a series of mono prenyloxycarbostyrils were synthesized and evaluated as potential inhibitors of soybean 15-Lipoxygenase (SLO) and their inhibitory potencies were compared to mono prenyloxycoumarins which had been reported in the previous works. The synthetic compounds inhibit lipoxygenase enzyme by competitive mechanism like the prenyloxy coumarins. The results showed that position and length of the prenyl moiety play the important role in lipoxygenase inhibitory activity. Among all of the synthetic compounds (coumarin and carbostyril derivatives), 5-farnesyloxycoumarin and 8-farnesyloxycarbostyril demonstrated the best inhibitory activity by IC50 values of 1.1 mu M and 0.53 mu M, respectively.

Automated summary

Catalyzed peroxidation of unsaturated lipids in animals and plants is closely related to the activity of 15-lipoxygenase enzymes. Lipoxygenases (LOXs) play important roles in various syndromes, and synthetic compounds showed potential as inhibitors of soybean 15-lipoxygenase. The position and length of the prenyl moiety were found to be crucial in lipoxygenase inhibitory activity, with 5-farnesyloxycoumarin and 8-farnesyloxycarbostyril demonstrating the best inhibitory activity.