Novel inhibitors of phenylalanine ammonia-lyase: 5-Aryl-1,3,4-oxathiazol-2- ones

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.