ANTICHOLINESTERASE ACTIVITY OF THE FUSARIUM METABOLITE VISOLTRICIN AND ITS N-METHYL DERIVATIVE

Visoltricin is a bioactive 4,5-disubstituted N-methylimidazole produce d by Fusarium tricinctum, which shows toxic activity towards Artemia s alina larvae and miotic activity on rabbit eye. The anticholinesterase properties and kinetic parameters of visoltricin and N-methyl visoltr icin were assessed. Visoltricin anticholinesterase activity was demons trated on human serum [median inhibitory concentration (IC50) = 2.6 x 10(-4) M], bovine erythrocyte acetylcholinesterase EC 3.1.1.7 (IC50 = 4 x 10(-4) M) and human serum cholinesterase EC 3.1.1.8 (IC50 = 1.9 x 10(-4) M). The acetylcholinesterase inhibition constants (K-i) of viso ltricin and N-methyl visoltricin were 1.88 x 10(-4) M and 6.5 x 10(-5) M, respectively. Kinetic studies showed for both compounds a mixed-ty pe inhibition, with partial binding of the inhibitor to the enzyme-sub strate complex. Visoltricin was a reversible inhibitor of acetylcholin esterase, as it was not hydrolysed by the inhibited enzyme, and the in hibition in vitro was concentration dependent but not time dependent. The anticholinesterase activity could explain, at least in part, the m iotic activity of visoltricin.