Novel Inhibitors of Phenylalanine Ammonia-lyase: 5-Aryl-1, 3, 4-oxathiazol-2-ones

Abstract

A series of 5‐aryl‐1,3,4‐oxathiazol‐2‐ones was synthesized and tested for inhibition against phenylalanine ammonia‐lyase (PAL) derived from the yeast Rhodotorula glutinis. All compounds inhibited PAL at 100 µM. Of the compounds tested, 5‐(4‐nitrophenyl)‐1,3,4‐oxathiazol‐2‐one (19) was the most effective, showing IC50 value of 2.5 µM, which was 2 times stronger than that of N‐(aminooxy) acetyl‐2,5‐dichloroaniline (Z302), a known PAL inhibitor. Compound 19 behaved as a noncompetitive inhibitor of PAL. When potato tuber disks were treated with 19 in the presence of laminarin, a β ‐1,3‐glucooligosaccharide elicitor, the amount of trans‐cinnamic acid diminished after 48 hr, being consistent with an effective inhibition of PAL. Most of the compounds inhibited the growth of lettuce seedlings at 100‐500 µM. However, no correlation was observed between the ability of 5‐aryl‐1,3,4‐oxathiazol‐2‐ones to inhibit PAL derived from R. glutinis and growth inhibitory activity against lettuce seedlings.