The effect of various acrylonitriles and related compounds on prostaglandin biosynthesis.
We have studied the effect of nearly 90 arylacrylonitrile derivatives, and several related compounds, on the biosynthesis of prostaglandins from bovine seminal vesicle microsomes. This effect was compared to that of triarylacrylonitrile derivatives known for their inhibiting properties. Several arylacrylonitrile derivatives have also proved good inhibitors, especially certain N-trisubstituted compounds: trans (dimethylamino-4 phenyl)-3 (methoxy-4' phenyl)-2 acrylonitrile was the best inhibitor of the group, with an IC50 of 0.07 microM. The absence of carboxy groups in these derivatives precludes the application of any of the site-models proposed to date. We suggest that the electronic charges carried especially by the three aromatic rings play an important role in the inhibiting mechanism.
D000181:Acrylonitrile / Q000031:analogs & derivatives / Q000494:pharmacology*; D000818:Animals; D002417:Cattle; D055598:Chemical Phenomena; D002621:Chemistry; D008297:Male; D008861:Microsomes / Q000378:metabolism; D009570:Nitriles / Q000494:pharmacology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011453:Prostaglandins / Q000096:biosynthesis*; D012669:Seminal Vesicles / Q000378:metabolism*; D013329:Structure-Activity Relationship
D009570:Nitriles; D011453:Prostaglandins; D011451:Prostaglandin-Endoperoxide Synthases; D000181:Acrylonitrile