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 of the natural compound ajoene, which is a bioactive natural product obtained from rearrangement of the unstable and reactive organosulfur compound allicin produced when garlic is freshly crushed. BisPMB has been shown to have superior cancer-cell cytotoxicity compared with ajoene and a modest selectivity towards cancer cells over non-cancerous ones. In this study, the inhibition effects of E / Z -bisPMB and Z -bisPMB 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 similar inhibition profiles against the four enzymes tested, with the IC 50 values ranging from 10.9 to 439.7 nM and the K i values ranging from 5.4 to 195.4 nM. Furthermore, bisPMB was more potent at inhibiting CA I, CA II and AChE compared with commercially available inhibitors.