Inhibition of Carbonic Anhydrase, Acetylcholinesterase and Butyrylcholinesterase by BisPMB, A Synthetic Analogue of Ajoene

Abstract

BisPMB (1,8-(bis-p-methoxyphenyl)-2,3,7-trithiaocta-4-ene-7-oxide) is a synthetic analogue ofthe natural compound ajoene, which is a bioactive natural product obtained from the rearrangement of theunstable and reactive organosulfur compound allicin produced when garlic is freshly crushed. BisPMB hasbeen shown to have superior cancer-cell cytotoxicity compared with ajoene and a modest selectivitytowards cancer cells over non-cancerous ones. In this study, the inhibition effects of E/Z-bisPMB and ZbisPMB against human carbonic anhydrase isozymes I and II (hCA I and II), acetylcholinesterase (AChE)and butyrylcholinesterase (BuChE) were investigated in which E/Z-bisPMB and Z-bisPMB showed similarinhibition profiles against the four enzymes tested, with the IC50values ranging from 10.9 to 439.7 nM andthe Ki values ranging from 5.4 to 195.4 nM. Furthermore, bisPMB was more potent at inhibiting CA I, CA IIand AChE compared with commercially available inhibitors.