Anticholinesterase activity of the fusarium metabolite visoltricin and its N-methyl derivative

Abstract

Visoltricin is a bioactive 4,5-disubstituted N-methylimidazole produced by Fusarium tricinctum, which shows toxic activity towards Artemia salina larvae and miotic activity on rabbit eye. The anticholinesterase properties and kinetic parameters of visoltricin and N-methyl visoltricin were assessed. Visoltricin anticholinesterase activity was demonstrated on human serum [median inhibitory concentration (IC 50) = 2.6 × 10 −4 m], bovine erythrocyte acetylcholinesterase EC 3.1.1.7 (IC 50 = 4 × 10 −4 m) and human serum cholinesterase EC 3.1.1.8 (IC 50 = 1.9 × 10 −4 m). The acetylcholinesterase inhibition constants ( K i) of visoltricin and N-methyl visoltricin were 1.88 × 10 −4 m, respectively. Kinetic studies showed for both compounds a mixed-type inhibition, with partial binding of the inhibitor to the enzyme-substrate complex. Visoltricin was a reversible inhibitor of acetylcholinesterase, as it was not hydrolysed by the inhibited enzyme, and the inhibition in vitro was concentration dependent but not time dependent. The anticholinesterase activity could explain, at least in part, the miotic activity of visoltricin.