1,3-Disubstituted p-tert-butylcalix[4]arenes as cholinesterase inhibitors

The inhibitory effect of 1,3-substituted p-tert-butylcalix[4]arenes on buty rylcholinesterase from horse serum has been discovered and kinetically inve stigated with photometric microassay techniques. The interaction of calix[4 ]arene with the enzyme is described in accordance with the formal kinetics of competitive reversible inhibition. The inhibition constants calculated d epend on the substituent in the lower rim of the calix[4]arene and vary in the range of (5-110) x 10(-6) M. The proposed mechanism of inhibition invol ves the cooperative interaction of indophenyl acetate used as a substrate, calix[4]arene and the enzyme without any covalent or electrostatic binding of the functional groups in the active site of cholinesterase. This results in the coordination of the calixarene on the enzyme surface in the proximi ty of the enzyme active site. Such interaction prevents the substrate from entering the enzyme active site.